TY  - JOUR
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Lazarević, Milica
AU  - Ignjatović, Đurđica
AU  - Tomić, Mirko
AU  - Nikolovski, Neda
AU  - Bjelobaba, Ivana
AU  - Momčilović, Miljana
AU  - Dimitrijević, Mirjana
AU  - Miljković, Đorđe
AU  - Stanisavljević, Suzana
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6643
AB  - We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.
PB  - Elsevier
T2  - Immunology Letters
T1  - Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate
VL  - 267
DO  - 10.1016/j.imlet.2024.106852
SP  - 106852
ER  - 

@article{
author = "Stegnjaić, Goran and Jevtić, Bojan and Lazarević, Milica and Ignjatović, Đurđica and Tomić, Mirko and Nikolovski, Neda and Bjelobaba, Ivana and Momčilović, Miljana and Dimitrijević, Mirjana and Miljković, Đorđe and Stanisavljević, Suzana",
year = "2024",
abstract = "We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.",
publisher = "Elsevier",
journal = "Immunology Letters",
title = "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate",
volume = "267",
doi = "10.1016/j.imlet.2024.106852",
pages = "106852"
}

Stegnjaić, G., Jevtić, B., Lazarević, M., Ignjatović, Đ., Tomić, M., Nikolovski, N., Bjelobaba, I., Momčilović, M., Dimitrijević, M., Miljković, Đ.,& Stanisavljević, S.. (2024). Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters
Elsevier., 267, 106852.
https://doi.org/10.1016/j.imlet.2024.106852

Stegnjaić G, Jevtić B, Lazarević M, Ignjatović Đ, Tomić M, Nikolovski N, Bjelobaba I, Momčilović M, Dimitrijević M, Miljković Đ, Stanisavljević S. Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters. 2024;267:106852.
doi:10.1016/j.imlet.2024.106852 .

Stegnjaić, Goran, Jevtić, Bojan, Lazarević, Milica, Ignjatović, Đurđica, Tomić, Mirko, Nikolovski, Neda, Bjelobaba, Ivana, Momčilović, Miljana, Dimitrijević, Mirjana, Miljković, Đorđe, Stanisavljević, Suzana, "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate" in Immunology Letters, 267 (2024):106852,
https://doi.org/10.1016/j.imlet.2024.106852 . .

TY  - JOUR
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Lazarević, Milica
AU  - Ignjatović, Đurđica
AU  - Tomić, Mirko
AU  - Nikolovski, Neda
AU  - Bjelobaba, Ivana
AU  - Momčilović, Miljana
AU  - Dimitrijević, Mirjana
AU  - Miljković, Đorđe
AU  - Stanisavljević, Suzana
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6644
AB  - We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.
PB  - Elsevier
T2  - Immunology Letters
T1  - Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate
VL  - 267
DO  - 10.1016/j.imlet.2024.106852
SP  - 106852
ER  - 

@article{
author = "Stegnjaić, Goran and Jevtić, Bojan and Lazarević, Milica and Ignjatović, Đurđica and Tomić, Mirko and Nikolovski, Neda and Bjelobaba, Ivana and Momčilović, Miljana and Dimitrijević, Mirjana and Miljković, Đorđe and Stanisavljević, Suzana",
year = "2024",
abstract = "We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.",
publisher = "Elsevier",
journal = "Immunology Letters",
title = "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate",
volume = "267",
doi = "10.1016/j.imlet.2024.106852",
pages = "106852"
}

Stegnjaić, G., Jevtić, B., Lazarević, M., Ignjatović, Đ., Tomić, M., Nikolovski, N., Bjelobaba, I., Momčilović, M., Dimitrijević, M., Miljković, Đ.,& Stanisavljević, S.. (2024). Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters
Elsevier., 267, 106852.
https://doi.org/10.1016/j.imlet.2024.106852

Stegnjaić G, Jevtić B, Lazarević M, Ignjatović Đ, Tomić M, Nikolovski N, Bjelobaba I, Momčilović M, Dimitrijević M, Miljković Đ, Stanisavljević S. Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters. 2024;267:106852.
doi:10.1016/j.imlet.2024.106852 .

Stegnjaić, Goran, Jevtić, Bojan, Lazarević, Milica, Ignjatović, Đurđica, Tomić, Mirko, Nikolovski, Neda, Bjelobaba, Ivana, Momčilović, Miljana, Dimitrijević, Mirjana, Miljković, Đorđe, Stanisavljević, Suzana, "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate" in Immunology Letters, 267 (2024):106852,
https://doi.org/10.1016/j.imlet.2024.106852 . .

TY  - JOUR
AU  - Lazarević, Milica
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Despotović, Sanja
AU  - Ignjatović, Đurđica
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Fraser, Graeme L
AU  - Dimitrijević, Mirjana
AU  - Miljković, Đorđe
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6501
AB  - Experimental autoimmune encephalomyelitis (EAE) induced in inbred rodents, i.e., genetically identical animals kept under identical environmental conditions, shows variable clinical outcomes. We investigated such variations of EAE in Dark Agouti rats immunized with spinal cord homogenate and identified four groups: lethal, severe, moderate, and mild, at day 28 post immunization. Higher numbers of CD4+ T cells, helper T cells type 1 (Th1) and 17 (Th17) in particular, were detected in the spinal cord of the severe group in comparison with the moderate group. In addition, increased proportion of Th1 and Th17 cells, and heightened levels of interferon (IFN)-γ and interleukin (IL)-6 were detected in the small intestine lamina propria of the severe group. A selective agonist of free fatty acid receptor type 2 (Ffar2) applied orally in the inductive phase of EAE shifted the distribution of the disease outcomes towards milder forms. This effect was paralleled with potentiation of intestinal innate lymphoid cells type 3 (ILC3) regulatory properties, and diminished Th1 and Th17 cell response in the lymph nodes draining the site of immunization. Our results suggest that different clinical outcomes in DA rats are under determinative influence of intestinal ILC3 activity during the inductive phase of EAE.
PB  - Springer Nature
T2  - Journal of Neuroinflammation
T1  - Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity
VL  - 21
DO  - 10.1186/s12974-024-03017-7
SP  - 26
ER  - 

@article{
author = "Lazarević, Milica and Stegnjaić, Goran and Jevtić, Bojan and Despotović, Sanja and Ignjatović, Đurđica and Stanisavljević, Suzana and Nikolovski, Neda and Momčilović, Miljana and Fraser, Graeme L and Dimitrijević, Mirjana and Miljković, Đorđe",
year = "2024",
abstract = "Experimental autoimmune encephalomyelitis (EAE) induced in inbred rodents, i.e., genetically identical animals kept under identical environmental conditions, shows variable clinical outcomes. We investigated such variations of EAE in Dark Agouti rats immunized with spinal cord homogenate and identified four groups: lethal, severe, moderate, and mild, at day 28 post immunization. Higher numbers of CD4+ T cells, helper T cells type 1 (Th1) and 17 (Th17) in particular, were detected in the spinal cord of the severe group in comparison with the moderate group. In addition, increased proportion of Th1 and Th17 cells, and heightened levels of interferon (IFN)-γ and interleukin (IL)-6 were detected in the small intestine lamina propria of the severe group. A selective agonist of free fatty acid receptor type 2 (Ffar2) applied orally in the inductive phase of EAE shifted the distribution of the disease outcomes towards milder forms. This effect was paralleled with potentiation of intestinal innate lymphoid cells type 3 (ILC3) regulatory properties, and diminished Th1 and Th17 cell response in the lymph nodes draining the site of immunization. Our results suggest that different clinical outcomes in DA rats are under determinative influence of intestinal ILC3 activity during the inductive phase of EAE.",
publisher = "Springer Nature",
journal = "Journal of Neuroinflammation",
title = "Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity",
volume = "21",
doi = "10.1186/s12974-024-03017-7",
pages = "26"
}

Lazarević, M., Stegnjaić, G., Jevtić, B., Despotović, S., Ignjatović, Đ., Stanisavljević, S., Nikolovski, N., Momčilović, M., Fraser, G. L., Dimitrijević, M.,& Miljković, Đ.. (2024). Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity. in Journal of Neuroinflammation
Springer Nature., 21, 26.
https://doi.org/10.1186/s12974-024-03017-7

Lazarević M, Stegnjaić G, Jevtić B, Despotović S, Ignjatović Đ, Stanisavljević S, Nikolovski N, Momčilović M, Fraser GL, Dimitrijević M, Miljković Đ. Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity. in Journal of Neuroinflammation. 2024;21:26.
doi:10.1186/s12974-024-03017-7 .

Lazarević, Milica, Stegnjaić, Goran, Jevtić, Bojan, Despotović, Sanja, Ignjatović, Đurđica, Stanisavljević, Suzana, Nikolovski, Neda, Momčilović, Miljana, Fraser, Graeme L, Dimitrijević, Mirjana, Miljković, Đorđe, "Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity" in Journal of Neuroinflammation, 21 (2024):26,
https://doi.org/10.1186/s12974-024-03017-7 . .

TY  - CONF
AU  - Mićanović, Dragica
AU  - Stegnjaić, Goran
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Foresti, Roberta
AU  - Motterlini, Roberto
AU  - Miljković, Đorđe
AU  - Saksida, Tamara
PY  - 2023
UR  - https://benbedphar.org/wp-content/uploads/2023/10/abstract_book_Graz_final.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6473
AB  - Type 1 diabetes (T1D) is an autoimmune disease that leads to the death of insulin-producing
pancreatic β-cells. The autoimmune response in T1D becomes chronic as a consequence of
regulatory mechanisms unable to counteract this disease. In this study, we evaluated the
anti-diabetic potential of a new hybrid compound (HYCO-3) consisting of a CO-releasing
molecule conjugated to a fumaric ester derivative that is known to activate the Nrf2 and
increase the expression of the CO-producing enzyme heme oxygenase-1. T1D was induced
in C57BL/6 mice treated intraperitoneally for 5 consecutive days with multiple low doses of
streptozotocin (40 mg/kg BW). HYCO-3 (25 mg/kg BW daily) was administered by oral
gavage while the control group received the vehicle (DMSO/sesame oil) for 14 days, starting
on the first day of streptozotocin treatment. To evaluate the development of T1D, glycaemia
and body mass were measured weekly. At the end of the experiment the pancreas was
collected and histochemical analyses for insulin expression were performed. Insulitis, the
infiltration of immune cells in the pancreas, was also assessed. We found that treatment
with HYCO-3 lowered blood glucose levels compared to the control group in association
with a lower insulitis grade and a higher expression of insulin in pancreatic islets.
Furthermore, to assess the effect of HYCO-3 on antigen specific response, cells from the
draining pancreatic lymph nodes of diabetic animals were stimulated with insulin and
HYCO-3 to assess the production of pro-inflammatory markers in cell supernatants. HYCO-
3 was able to down-regulate the production of IL-17 in the cultures where antigen specific
response was induced with insulin.
Overall, our results show that HYCO-3 ameliorated T1D in C57BL/6 mice by inhibiting the
recruitment of immune cells into the pancreas. These results warrant future investigation of
cellular and molecular mechanisms by which HYCO-3 acts on immune cells that are of
importance in the pathogenesis of T1D.
PB  - BenBedPhar Consortium
C3  - 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria
T1  - HYCO-3, an Nrf2 activator that simultaneously releases carbon monoxide (CO), ameliorates type 1 diabetes in a mouse model
SP  - 46
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6473
ER  - 

@conference{
author = "Mićanović, Dragica and Stegnjaić, Goran and Nikolovski, Neda and Momčilović, Miljana and Foresti, Roberta and Motterlini, Roberto and Miljković, Đorđe and Saksida, Tamara",
year = "2023",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease that leads to the death of insulin-producing
pancreatic β-cells. The autoimmune response in T1D becomes chronic as a consequence of
regulatory mechanisms unable to counteract this disease. In this study, we evaluated the
anti-diabetic potential of a new hybrid compound (HYCO-3) consisting of a CO-releasing
molecule conjugated to a fumaric ester derivative that is known to activate the Nrf2 and
increase the expression of the CO-producing enzyme heme oxygenase-1. T1D was induced
in C57BL/6 mice treated intraperitoneally for 5 consecutive days with multiple low doses of
streptozotocin (40 mg/kg BW). HYCO-3 (25 mg/kg BW daily) was administered by oral
gavage while the control group received the vehicle (DMSO/sesame oil) for 14 days, starting
on the first day of streptozotocin treatment. To evaluate the development of T1D, glycaemia
and body mass were measured weekly. At the end of the experiment the pancreas was
collected and histochemical analyses for insulin expression were performed. Insulitis, the
infiltration of immune cells in the pancreas, was also assessed. We found that treatment
with HYCO-3 lowered blood glucose levels compared to the control group in association
with a lower insulitis grade and a higher expression of insulin in pancreatic islets.
Furthermore, to assess the effect of HYCO-3 on antigen specific response, cells from the
draining pancreatic lymph nodes of diabetic animals were stimulated with insulin and
HYCO-3 to assess the production of pro-inflammatory markers in cell supernatants. HYCO-
3 was able to down-regulate the production of IL-17 in the cultures where antigen specific
response was induced with insulin.
Overall, our results show that HYCO-3 ameliorated T1D in C57BL/6 mice by inhibiting the
recruitment of immune cells into the pancreas. These results warrant future investigation of
cellular and molecular mechanisms by which HYCO-3 acts on immune cells that are of
importance in the pathogenesis of T1D.",
publisher = "BenBedPhar Consortium",
journal = "5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria",
title = "HYCO-3, an Nrf2 activator that simultaneously releases carbon monoxide (CO), ameliorates type 1 diabetes in a mouse model",
pages = "46",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6473"
}

Mićanović, D., Stegnjaić, G., Nikolovski, N., Momčilović, M., Foresti, R., Motterlini, R., Miljković, Đ.,& Saksida, T.. (2023). HYCO-3, an Nrf2 activator that simultaneously releases carbon monoxide (CO), ameliorates type 1 diabetes in a mouse model. in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria
BenBedPhar Consortium., 46.
https://hdl.handle.net/21.15107/rcub_ibiss_6473

Mićanović D, Stegnjaić G, Nikolovski N, Momčilović M, Foresti R, Motterlini R, Miljković Đ, Saksida T. HYCO-3, an Nrf2 activator that simultaneously releases carbon monoxide (CO), ameliorates type 1 diabetes in a mouse model. in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria. 2023;:46.
https://hdl.handle.net/21.15107/rcub_ibiss_6473 .

Mićanović, Dragica, Stegnjaić, Goran, Nikolovski, Neda, Momčilović, Miljana, Foresti, Roberta, Motterlini, Roberto, Miljković, Đorđe, Saksida, Tamara, "HYCO-3, an Nrf2 activator that simultaneously releases carbon monoxide (CO), ameliorates type 1 diabetes in a mouse model" in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria (2023):46,
https://hdl.handle.net/21.15107/rcub_ibiss_6473 .

TY  - CONF
AU  - Stegnjaić, Goran
AU  - Mićanović, Dragica
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Saksida, Tamara
AU  - Foresti, Roberta
AU  - Motterlini, Roberto
AU  - Miljković, Đorđe
PY  - 2023
UR  - https://benbedphar.org/wp-content/uploads/2023/10/abstract_book_Graz_final.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6476
AB  - HYCOs are a novel class of hybrid compounds consisting of fumaric esters conjugated to
carbon monoxide-releasing molecules (CO-RMs). They were designed based on the
consideration that fumaric esters are known to activate the transcription factor Nrf2 and that
CO possesses potent anti-inflammatory properties. The dual action of these hybrids has
shown promising therapeutic effects. in animal models of psoriasis and multiple sclerosis.
We have recently started with the group of Drs Motterlini and Foresti in France a
collaborative research project relevant to the BenBedPhar COST Action, focusing on the
immunomodulatory effects of HYCOs. These effects were examined in vitro in cultures of
myeloid-derived cells (macrophages and dendritic cells), lymph node cells, immune cells
isolated from the inflamed central nervous system, and microglia. By assessing the
production of immunoactive molecules, including nitric oxide, reactive oxygen species and
cytokines, we provide evidence that HYCOs display immunomodulatory effects in all cell
populations examined in vitro. Moreover, we were able to demonstrate that HYCOs are
efficient in ameliorating type 1 diabetes in an animal model of this autoimmune disease. Our
results indicate that HYCOs are Nrf2 activators with promising immunomodulatory
therapeutic properties.
PB  - BenBedPhar Consortium
C3  - 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria
T1  - Immunomodulatory properties of HYCOs, NRF2 activators that simultaneously release carbon monoxide (CO) to cells and tissues
SP  - 21
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6476
ER  - 

@conference{
author = "Stegnjaić, Goran and Mićanović, Dragica and Nikolovski, Neda and Momčilović, Miljana and Saksida, Tamara and Foresti, Roberta and Motterlini, Roberto and Miljković, Đorđe",
year = "2023",
abstract = "HYCOs are a novel class of hybrid compounds consisting of fumaric esters conjugated to
carbon monoxide-releasing molecules (CO-RMs). They were designed based on the
consideration that fumaric esters are known to activate the transcription factor Nrf2 and that
CO possesses potent anti-inflammatory properties. The dual action of these hybrids has
shown promising therapeutic effects. in animal models of psoriasis and multiple sclerosis.
We have recently started with the group of Drs Motterlini and Foresti in France a
collaborative research project relevant to the BenBedPhar COST Action, focusing on the
immunomodulatory effects of HYCOs. These effects were examined in vitro in cultures of
myeloid-derived cells (macrophages and dendritic cells), lymph node cells, immune cells
isolated from the inflamed central nervous system, and microglia. By assessing the
production of immunoactive molecules, including nitric oxide, reactive oxygen species and
cytokines, we provide evidence that HYCOs display immunomodulatory effects in all cell
populations examined in vitro. Moreover, we were able to demonstrate that HYCOs are
efficient in ameliorating type 1 diabetes in an animal model of this autoimmune disease. Our
results indicate that HYCOs are Nrf2 activators with promising immunomodulatory
therapeutic properties.",
publisher = "BenBedPhar Consortium",
journal = "5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria",
title = "Immunomodulatory properties of HYCOs, NRF2 activators that simultaneously release carbon monoxide (CO) to cells and tissues",
pages = "21",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6476"
}

Stegnjaić, G., Mićanović, D., Nikolovski, N., Momčilović, M., Saksida, T., Foresti, R., Motterlini, R.,& Miljković, Đ.. (2023). Immunomodulatory properties of HYCOs, NRF2 activators that simultaneously release carbon monoxide (CO) to cells and tissues. in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria
BenBedPhar Consortium., 21.
https://hdl.handle.net/21.15107/rcub_ibiss_6476

Stegnjaić G, Mićanović D, Nikolovski N, Momčilović M, Saksida T, Foresti R, Motterlini R, Miljković Đ. Immunomodulatory properties of HYCOs, NRF2 activators that simultaneously release carbon monoxide (CO) to cells and tissues. in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria. 2023;:21.
https://hdl.handle.net/21.15107/rcub_ibiss_6476 .

Stegnjaić, Goran, Mićanović, Dragica, Nikolovski, Neda, Momčilović, Miljana, Saksida, Tamara, Foresti, Roberta, Motterlini, Roberto, Miljković, Đorđe, "Immunomodulatory properties of HYCOs, NRF2 activators that simultaneously release carbon monoxide (CO) to cells and tissues" in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria (2023):21,
https://hdl.handle.net/21.15107/rcub_ibiss_6476 .

TY  - CONF
AU  - Stegnjaić, Goran
AU  - Lazarević, Milica
AU  - Jevtić, Bojan
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Mostarica Stojković, Marija
AU  - Miljković, Đorđe
AU  - Dimitrijević, Mirjana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6363
AB  - Experimental autoimmune encephalomyelitis (EAE) in inbred rodents commonly shows different clinical courses, so that the diseased animals can be clustered into four groups: mild. moderate, severe and lethal. Our aim was to determine biomolecular markers in the preclinical phase of EAE that allow the prediction of clinical course. 
Methods: Female Dark Agouti rats were immunized with spinal cord homogenate without adjuvant and examined for four weeks for clinical signs of EAE. Cells and sera from blood collected on days 0, 3, and 7 after immunization were processed for detection of proinflammatory cytokines (IL-1, IL-6, TNF, and IFN) by "real-time" RT-PCR and ELISA, respectively. 
Results: Induction of EAE resulted in the downregulation of IFN and TNF in the preclinical phase of disease, whereas IL-1 and IL-6 expression levels were unaffected. However, there was no correlation between the relative expression of IFN or TNF and the cumulative clinical score (sum of daily clinical scores), suggesting that they are not predictive markers of EAE severity. Our preliminary results that suggest a negative correlation between IL-1 expression level before EAE induction and cumulative score require further justification. 
Conclusion: The proinflammatory cytokines investigated so far in our study cannot be considered as good biomarkers of EAE severity. However, the downregulation of IFN and TNF in the blood cells during the asymptomatic phase of EAE suggests that they enter the central nervous system early from the bloodstream, which argues for the study of chemokine and/or chemokine receptors expression as potential biomarkers for the clinical courses of EAE.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate
SP  - 89
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6363
ER  - 

@conference{
author = "Stegnjaić, Goran and Lazarević, Milica and Jevtić, Bojan and Stanisavljević, Suzana and Nikolovski, Neda and Momčilović, Miljana and Mostarica Stojković, Marija and Miljković, Đorđe and Dimitrijević, Mirjana",
year = "2023",
abstract = "Experimental autoimmune encephalomyelitis (EAE) in inbred rodents commonly shows different clinical courses, so that the diseased animals can be clustered into four groups: mild. moderate, severe and lethal. Our aim was to determine biomolecular markers in the preclinical phase of EAE that allow the prediction of clinical course. 
Methods: Female Dark Agouti rats were immunized with spinal cord homogenate without adjuvant and examined for four weeks for clinical signs of EAE. Cells and sera from blood collected on days 0, 3, and 7 after immunization were processed for detection of proinflammatory cytokines (IL-1, IL-6, TNF, and IFN) by "real-time" RT-PCR and ELISA, respectively. 
Results: Induction of EAE resulted in the downregulation of IFN and TNF in the preclinical phase of disease, whereas IL-1 and IL-6 expression levels were unaffected. However, there was no correlation between the relative expression of IFN or TNF and the cumulative clinical score (sum of daily clinical scores), suggesting that they are not predictive markers of EAE severity. Our preliminary results that suggest a negative correlation between IL-1 expression level before EAE induction and cumulative score require further justification. 
Conclusion: The proinflammatory cytokines investigated so far in our study cannot be considered as good biomarkers of EAE severity. However, the downregulation of IFN and TNF in the blood cells during the asymptomatic phase of EAE suggests that they enter the central nervous system early from the bloodstream, which argues for the study of chemokine and/or chemokine receptors expression as potential biomarkers for the clinical courses of EAE.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate",
pages = "89",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6363"
}

Stegnjaić, G., Lazarević, M., Jevtić, B., Stanisavljević, S., Nikolovski, N., Momčilović, M., Mostarica Stojković, M., Miljković, Đ.,& Dimitrijević, M.. (2023). Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade., 89.
https://hdl.handle.net/21.15107/rcub_ibiss_6363

Stegnjaić G, Lazarević M, Jevtić B, Stanisavljević S, Nikolovski N, Momčilović M, Mostarica Stojković M, Miljković Đ, Dimitrijević M. Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:89.
https://hdl.handle.net/21.15107/rcub_ibiss_6363 .

Stegnjaić, Goran, Lazarević, Milica, Jevtić, Bojan, Stanisavljević, Suzana, Nikolovski, Neda, Momčilović, Miljana, Mostarica Stojković, Marija, Miljković, Đorđe, Dimitrijević, Mirjana, "Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):89,
https://hdl.handle.net/21.15107/rcub_ibiss_6363 .

TY  - CONF
AU  - Lazarević, Milica
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Dimitrijević, Mirjana
AU  - Miljković, Đorđe
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6300
AB  - Experimental autoimmune encephalomyelitis (EAE) is commonly induced with
central nervous system antigens mixed with complete Freund’s adjuvant (CFA). This
adjuvant has a confounding influence on the translational capacity of EAE as multiple
sclerosis (MS) model. Thus, we developed a novel subtype of EAE induced in Dark
Agouti (DA) rats with spinal cord homogenate (SCH) without CFA and characterized
it as a reliable MS model. Despite genetic homogeneity of experimental animals and
controlled environmental conditions, we observed variations in EAE clinical course in
SCH-immunized DA rats and four clinical groups were identified: lethal, severe,
moderate, and mild. Immune cells of spinal cord, small intestine lamina propria and
lymph nodes draining the site of immunization were compared between moderate and
severe group. Higher numbers of CD4+ T cells, regulatory T cells (Treg), helper T
cells type 1 (Th1) and 17 (Th17), and B cells were detected in the spinal cords of
severe group. Also, higher levels of interferon (IFN)-γ and interleukin (IL)-6 and an
increased proportion of Th1 and Th17 cells were detected in the lamina propria of the
severe group. Aminoguanidine – an inducible nitric oxide synthase inhibitor that was
applied to the rats during the effector phase of the disease ameliorated EAE and
imposed a shift of clinical outcomes towards milder variants. Our results suggest that
different clinical outcomes in DA rats come as a consequence of variability in the
strength of the effector mechanisms exerted within the CNS. The study of the
underlying mechanisms for the observed variability is necessary.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats
SP  - 42
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6300
ER  - 

@conference{
author = "Lazarević, Milica and Stegnjaić, Goran and Jevtić, Bojan and Stanisavljević, Suzana and Nikolovski, Neda and Momčilović, Miljana and Dimitrijević, Mirjana and Miljković, Đorđe",
year = "2023",
abstract = "Experimental autoimmune encephalomyelitis (EAE) is commonly induced with
central nervous system antigens mixed with complete Freund’s adjuvant (CFA). This
adjuvant has a confounding influence on the translational capacity of EAE as multiple
sclerosis (MS) model. Thus, we developed a novel subtype of EAE induced in Dark
Agouti (DA) rats with spinal cord homogenate (SCH) without CFA and characterized
it as a reliable MS model. Despite genetic homogeneity of experimental animals and
controlled environmental conditions, we observed variations in EAE clinical course in
SCH-immunized DA rats and four clinical groups were identified: lethal, severe,
moderate, and mild. Immune cells of spinal cord, small intestine lamina propria and
lymph nodes draining the site of immunization were compared between moderate and
severe group. Higher numbers of CD4+ T cells, regulatory T cells (Treg), helper T
cells type 1 (Th1) and 17 (Th17), and B cells were detected in the spinal cords of
severe group. Also, higher levels of interferon (IFN)-γ and interleukin (IL)-6 and an
increased proportion of Th1 and Th17 cells were detected in the lamina propria of the
severe group. Aminoguanidine – an inducible nitric oxide synthase inhibitor that was
applied to the rats during the effector phase of the disease ameliorated EAE and
imposed a shift of clinical outcomes towards milder variants. Our results suggest that
different clinical outcomes in DA rats come as a consequence of variability in the
strength of the effector mechanisms exerted within the CNS. The study of the
underlying mechanisms for the observed variability is necessary.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats",
pages = "42",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6300"
}

Lazarević, M., Stegnjaić, G., Jevtić, B., Stanisavljević, S., Nikolovski, N., Momčilović, M., Dimitrijević, M.,& Miljković, Đ.. (2023). Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 42.
https://hdl.handle.net/21.15107/rcub_ibiss_6300

Lazarević M, Stegnjaić G, Jevtić B, Stanisavljević S, Nikolovski N, Momčilović M, Dimitrijević M, Miljković Đ. Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:42.
https://hdl.handle.net/21.15107/rcub_ibiss_6300 .

Lazarević, Milica, Stegnjaić, Goran, Jevtić, Bojan, Stanisavljević, Suzana, Nikolovski, Neda, Momčilović, Miljana, Dimitrijević, Mirjana, Miljković, Đorđe, "Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats" in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):42,
https://hdl.handle.net/21.15107/rcub_ibiss_6300 .

TY  - JOUR
AU  - Stegnjaić, Goran
AU  - Tsiailanis, Antonios D.
AU  - Lazarević, Milica
AU  - Gkalpinos, Vasileios K.
AU  - Nikolovski, Neda
AU  - Antoniou, Thomas
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Momčilović, Miljana
AU  - Miljković, Đorđe
AU  - Tzakos, Andreas G.
AU  - Jevtić, Bojan
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5305
AB  - Gallic acid is a phenolic acid present in various plants, nuts, and fruits. It is well known for
its anti-oxidative and anti-inflammatory properties. The phenethyl ester of gallic acid (PEGA) was
synthesized with the aim of increasing the bioavailability of gallic acid, and thus its pharmacological
potential. Here, the effects of PEGA on encephalitogenic cells were examined, and PEGA was
found to modulate the inflammatory activities of T cells and macrophages/microglia. Specifically,
PEGA reduced the release of interleukin (IL)-17 and interferon (IFN)-γ from T cells, as well as NO,
and IL-6 from macrophages/microglia. Importantly, PEGA ameliorated experimental autoimmune
encephalomyelitis, an animal model of chronic inflammatory disease of the central nervous system
(CNS)—multiple sclerosis. Thus, PEGA is a potent anti-inflammatory compound with a perspective
to be further explored in the context of CNS autoimmunity and other chronic inflammatory disorders.
PB  - Basel: MDPI
T2  - Molecules
T1  - Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis
IS  - 24
VL  - 27
DO  - 10.3390/molecules27248770
SP  - 8770
ER  - 

@article{
author = "Stegnjaić, Goran and Tsiailanis, Antonios D. and Lazarević, Milica and Gkalpinos, Vasileios K. and Nikolovski, Neda and Antoniou, Thomas and Stanisavljević, Suzana and Dimitrijević, Mirjana and Momčilović, Miljana and Miljković, Đorđe and Tzakos, Andreas G. and Jevtić, Bojan",
year = "2022",
abstract = "Gallic acid is a phenolic acid present in various plants, nuts, and fruits. It is well known for
its anti-oxidative and anti-inflammatory properties. The phenethyl ester of gallic acid (PEGA) was
synthesized with the aim of increasing the bioavailability of gallic acid, and thus its pharmacological
potential. Here, the effects of PEGA on encephalitogenic cells were examined, and PEGA was
found to modulate the inflammatory activities of T cells and macrophages/microglia. Specifically,
PEGA reduced the release of interleukin (IL)-17 and interferon (IFN)-γ from T cells, as well as NO,
and IL-6 from macrophages/microglia. Importantly, PEGA ameliorated experimental autoimmune
encephalomyelitis, an animal model of chronic inflammatory disease of the central nervous system
(CNS)—multiple sclerosis. Thus, PEGA is a potent anti-inflammatory compound with a perspective
to be further explored in the context of CNS autoimmunity and other chronic inflammatory disorders.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis",
number = "24",
volume = "27",
doi = "10.3390/molecules27248770",
pages = "8770"
}

Stegnjaić, G., Tsiailanis, A. D., Lazarević, M., Gkalpinos, V. K., Nikolovski, N., Antoniou, T., Stanisavljević, S., Dimitrijević, M., Momčilović, M., Miljković, Đ., Tzakos, A. G.,& Jevtić, B.. (2022). Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis. in Molecules
Basel: MDPI., 27(24), 8770.
https://doi.org/10.3390/molecules27248770

Stegnjaić G, Tsiailanis AD, Lazarević M, Gkalpinos VK, Nikolovski N, Antoniou T, Stanisavljević S, Dimitrijević M, Momčilović M, Miljković Đ, Tzakos AG, Jevtić B. Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis. in Molecules. 2022;27(24):8770.
doi:10.3390/molecules27248770 .

Stegnjaić, Goran, Tsiailanis, Antonios D., Lazarević, Milica, Gkalpinos, Vasileios K., Nikolovski, Neda, Antoniou, Thomas, Stanisavljević, Suzana, Dimitrijević, Mirjana, Momčilović, Miljana, Miljković, Đorđe, Tzakos, Andreas G., Jevtić, Bojan, "Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis" in Molecules, 27, no. 24 (2022):8770,
https://doi.org/10.3390/molecules27248770 . .

TY  - CONF
AU  - Stegnjaić, Goran
AU  - Lazarević, Milica
AU  - Tsiailanis, Antonios D
AU  - Antoniou, Thomas
AU  - Gkalpinos, Vasileios K
AU  - Nikolovski, Neda
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Momčilović, Miljana
AU  - Miljković, Đorđe
AU  - Tzakos, Andreas G
AU  - Jevtić, Bojan
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6299
AB  - This study aimed to evaluate the effects of a synthetic gallic acid (GA) derivative in the
central nervous system (CNS) autoimmunity, i.e. in experimental autoimmune
encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced in DA
rats by injection of autologous spinal cord homogenate, with a gallic acid derivative being
applied subcutaneously (20 mg/kg, day 7-22 post-immunization). GA derivative
ameliorated EAE. Cells from lymph nodes draining the site of immunization (DLNC),
isolated in the inductive phase of the disease, and spinal cord immune cells (SCIC),
isolated at the peak of disease, were exposed to GA derivative in vitro. Encephalitogenic
cytokines, interferon (IFN)-γ and interleukin (IL)-17, were decreased in SCIC and DLNC
under the influence of GA derivative. The proportion of IL-17-producing CD4+ T cells was
reduced in SCIC (flow cytometry). Treatment of microglial BV2 cells with GA derivative
led to inhibition of NO, IL-6, and tumor necrosis factor release. These results imply that
the synthesized GA derivative is a potent immunomodulator, able to ameliorate EAE. Its
effects on the CNS autoimmunity are related to the inhibition of encephalitogenic T cells
and macrophage/microglia activity in our study.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - The effect of a gallic acid derivative on encephalitogenic cells
SP  - 140
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6299
ER  - 

@conference{
author = "Stegnjaić, Goran and Lazarević, Milica and Tsiailanis, Antonios D and Antoniou, Thomas and Gkalpinos, Vasileios K and Nikolovski, Neda and Stanisavljević, Suzana and Dimitrijević, Mirjana and Momčilović, Miljana and Miljković, Đorđe and Tzakos, Andreas G and Jevtić, Bojan",
year = "2022",
abstract = "This study aimed to evaluate the effects of a synthetic gallic acid (GA) derivative in the
central nervous system (CNS) autoimmunity, i.e. in experimental autoimmune
encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced in DA
rats by injection of autologous spinal cord homogenate, with a gallic acid derivative being
applied subcutaneously (20 mg/kg, day 7-22 post-immunization). GA derivative
ameliorated EAE. Cells from lymph nodes draining the site of immunization (DLNC),
isolated in the inductive phase of the disease, and spinal cord immune cells (SCIC),
isolated at the peak of disease, were exposed to GA derivative in vitro. Encephalitogenic
cytokines, interferon (IFN)-γ and interleukin (IL)-17, were decreased in SCIC and DLNC
under the influence of GA derivative. The proportion of IL-17-producing CD4+ T cells was
reduced in SCIC (flow cytometry). Treatment of microglial BV2 cells with GA derivative
led to inhibition of NO, IL-6, and tumor necrosis factor release. These results imply that
the synthesized GA derivative is a potent immunomodulator, able to ameliorate EAE. Its
effects on the CNS autoimmunity are related to the inhibition of encephalitogenic T cells
and macrophage/microglia activity in our study.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "The effect of a gallic acid derivative on encephalitogenic cells",
pages = "140",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6299"
}

Stegnjaić, G., Lazarević, M., Tsiailanis, A. D., Antoniou, T., Gkalpinos, V. K., Nikolovski, N., Stanisavljević, S., Dimitrijević, M., Momčilović, M., Miljković, Đ., Tzakos, A. G.,& Jevtić, B.. (2022). The effect of a gallic acid derivative on encephalitogenic cells. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 140.
https://hdl.handle.net/21.15107/rcub_ibiss_6299

Stegnjaić G, Lazarević M, Tsiailanis AD, Antoniou T, Gkalpinos VK, Nikolovski N, Stanisavljević S, Dimitrijević M, Momčilović M, Miljković Đ, Tzakos AG, Jevtić B. The effect of a gallic acid derivative on encephalitogenic cells. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:140.
https://hdl.handle.net/21.15107/rcub_ibiss_6299 .

Stegnjaić, Goran, Lazarević, Milica, Tsiailanis, Antonios D, Antoniou, Thomas, Gkalpinos, Vasileios K, Nikolovski, Neda, Stanisavljević, Suzana, Dimitrijević, Mirjana, Momčilović, Miljana, Miljković, Đorđe, Tzakos, Andreas G, Jevtić, Bojan, "The effect of a gallic acid derivative on encephalitogenic cells" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):140,
https://hdl.handle.net/21.15107/rcub_ibiss_6299 .

TY  - CONF
AU  - Mićanović, Dragica
AU  - Nikolovski, Neda
AU  - Koprivica, Ivan
AU  - Despotović, Sanja
AU  - Jevtić, Bojan
AU  - Stanisavljević, Suzana
AU  - Momčilović, Miljana
AU  - Pejnović, Nada
AU  - Stojanović, Ivana D.
AU  - Miljković, Đorđe
AU  - Saksida, Tamara
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5770
AB  - Примена етил-пирувата у третману аутоимунских болести је испитивана
у анималним моделима дијабетеса типа 1, мултипле склерозе и
миокардитиса. Показало се да етил-пируват ефикасно делује против
аутоимунских процеса и следствено доводи до побољшања клиничке
слике у овим моделима. Као главне мете деловања овог једињења
идентификоване су дендритске ћелије и Т лимфоцити. Утврђено је да
етил пируват потенцира толерогена својства денритских ћелија, као и
регулаторне Т лимфоците, a да инхибира ефекторске функције макрофага
и ограничава активацију и функцију ефекторских Т лимфоцита.
Инхибиторно дејство етил-пирувата на аутоимунске процесе је остварено
захваљујући његовим редокс и метаболичким ефектима, а пре свега
посредством његове интеракције са молекулом ХМГБ1. Имајући у виду да
су претходна истраживања показала да је примена етил-пирувата у људи
безбедна, будућа истраживања би морала бити усмерена ка транслацији
сазнања стечених у анималним моделима на терапијску примену овог
једињења у аутоимунским болестима.
AB  - Primena etil-piruvata u tretmanu autoimunskih bolesti je ispitivana u animalnim modelima dijabetesa tipa 1, multiple skleroze i miokarditisa. Pokazalo se da etil-piruvat efikasno deluje protiv autoimunskih procesa i sledstveno dovodi do poboljšanja kliničke slike u ovim modelima. Kao glavne mete delovanja ovog jedinjenja identifikovane su dendritske ćelije i T limfociti. Utvrđeno je da etil piruvat potencira tolerogena svojstva denritskih ćelija, kao i regulatorne T limfocite, a da inhibira efektorske funkcije makrofaga i ograničava aktivaciju i funkciju efektorskih T limfocita. Inhibitorno dejstvo etil-piruvata na autoimunske procese je ostvareno zahvaljujući njegovim redoks i metaboličkim efektima, a pre svega posredstvom njegove interakcije sa molekulom HMGB1. Imajući u vidu da su prethodna istraživanja pokazala da je primena etil-piruvata u ljudi bezbedna, buduća istraživanja bi morala biti usmerena ka translaciji saznanja stečenih u animalnim modelima na terapijsku primenu ovog jedinjenja u autoimunskim bolestima.
PB  - Belgrade: Serbian Academy of Sciences and Arts
C3  - Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia
T1  - Etil-piruvat i autoimunske bolesti
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5770
ER  - 

@conference{
author = "Mićanović, Dragica and Nikolovski, Neda and Koprivica, Ivan and Despotović, Sanja and Jevtić, Bojan and Stanisavljević, Suzana and Momčilović, Miljana and Pejnović, Nada and Stojanović, Ivana D. and Miljković, Đorđe and Saksida, Tamara",
year = "2022",
abstract = "Примена етил-пирувата у третману аутоимунских болести је испитивана
у анималним моделима дијабетеса типа 1, мултипле склерозе и
миокардитиса. Показало се да етил-пируват ефикасно делује против
аутоимунских процеса и следствено доводи до побољшања клиничке
слике у овим моделима. Као главне мете деловања овог једињења
идентификоване су дендритске ћелије и Т лимфоцити. Утврђено је да
етил пируват потенцира толерогена својства денритских ћелија, као и
регулаторне Т лимфоците, a да инхибира ефекторске функције макрофага
и ограничава активацију и функцију ефекторских Т лимфоцита.
Инхибиторно дејство етил-пирувата на аутоимунске процесе је остварено
захваљујући његовим редокс и метаболичким ефектима, а пре свега
посредством његове интеракције са молекулом ХМГБ1. Имајући у виду да
су претходна истраживања показала да је примена етил-пирувата у људи
безбедна, будућа истраживања би морала бити усмерена ка транслацији
сазнања стечених у анималним моделима на терапијску примену овог
једињења у аутоимунским болестима., Primena etil-piruvata u tretmanu autoimunskih bolesti je ispitivana u animalnim modelima dijabetesa tipa 1, multiple skleroze i miokarditisa. Pokazalo se da etil-piruvat efikasno deluje protiv autoimunskih procesa i sledstveno dovodi do poboljšanja kliničke slike u ovim modelima. Kao glavne mete delovanja ovog jedinjenja identifikovane su dendritske ćelije i T limfociti. Utvrđeno je da etil piruvat potencira tolerogena svojstva denritskih ćelija, kao i regulatorne T limfocite, a da inhibira efektorske funkcije makrofaga i ograničava aktivaciju i funkciju efektorskih T limfocita. Inhibitorno dejstvo etil-piruvata na autoimunske procese je ostvareno zahvaljujući njegovim redoks i metaboličkim efektima, a pre svega posredstvom njegove interakcije sa molekulom HMGB1. Imajući u vidu da su prethodna istraživanja pokazala da je primena etil-piruvata u ljudi bezbedna, buduća istraživanja bi morala biti usmerena ka translaciji saznanja stečenih u animalnim modelima na terapijsku primenu ovog jedinjenja u autoimunskim bolestima.",
publisher = "Belgrade: Serbian Academy of Sciences and Arts",
journal = "Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia",
title = "Etil-piruvat i autoimunske bolesti",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5770"
}

Mićanović, D., Nikolovski, N., Koprivica, I., Despotović, S., Jevtić, B., Stanisavljević, S., Momčilović, M., Pejnović, N., Stojanović, I. D., Miljković, Đ.,& Saksida, T.. (2022). Etil-piruvat i autoimunske bolesti. in Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia
Belgrade: Serbian Academy of Sciences and Arts..
https://hdl.handle.net/21.15107/rcub_ibiss_5770

Mićanović D, Nikolovski N, Koprivica I, Despotović S, Jevtić B, Stanisavljević S, Momčilović M, Pejnović N, Stojanović ID, Miljković Đ, Saksida T. Etil-piruvat i autoimunske bolesti. in Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5770 .

Mićanović, Dragica, Nikolovski, Neda, Koprivica, Ivan, Despotović, Sanja, Jevtić, Bojan, Stanisavljević, Suzana, Momčilović, Miljana, Pejnović, Nada, Stojanović, Ivana D., Miljković, Đorđe, Saksida, Tamara, "Etil-piruvat i autoimunske bolesti" in Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5770 .

TY  - JOUR
AU  - Stegnjaić, Goran
AU  - Lazarević, Milica
AU  - Diamantis, Dimitrois A
AU  - Nikolovski, Neda
AU  - Jevtić, Bojan
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Momčilović, Miljana
AU  - Tzakos, Andreas G
AU  - Miljković, Đorđe
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5085
AB  - Rosmarinic acid is a polyphenolic compound, abundantly present in herbs of the Lamiaceae family. The aim of
the study was to evaluate the immunomodulatory properties of a recently developed phenethyl ester derivative
of rosmarinic acid (PERA), with enhanced ability of diffusion through biological membranes, in an animal model
of the central nervous system (CNS) autoimmunity. To this end, experimental autoimmune encephalomyelitis
(EAE), an animal model of multiple sclerosis was used. Daily subcutaneous administration of PERA (30 mg/kg)
from day 7 to day 22 after immunization successfully ameliorated EAE induced in Dark Agouti rats, shortening
the disease duration and reducing maximal, cumulative and mean clinical score. PERA efficiently reduced
production of major encephalitogenic cytokines, interferon (IFN)-γ and interleukin (IL)-17, in immune cells from
the CNS or the lymph nodes draining the site of immunization of EAE rats, as well as in CD4+ T cells purified
from the lymph nodes. Also, PERA inhibited NO production in the CNS and the lymph nodes, as well as in
macrophages and microglial cells. Finally, microglial ability to produce pro-inflammatory cytokines IL-6, and
tumor necrosis factor (TNF) were also reduced by PERA. Our results clearly imply that PERA possesses antiencephalitogenic properties. Thus, further studies on the relevance of the observed effects for the therapy of
multiple sclerosis are warranted.
PB  - Amsterdam : Elsevier
T2  - Immunology Letters
T1  - Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis
VL  - 251-252
DO  - 10.1016/j.imlet.2022.09.006
SP  - 9
EP  - 19
ER  - 

@article{
author = "Stegnjaić, Goran and Lazarević, Milica and Diamantis, Dimitrois A and Nikolovski, Neda and Jevtić, Bojan and Stanisavljević, Suzana and Dimitrijević, Mirjana and Momčilović, Miljana and Tzakos, Andreas G and Miljković, Đorđe",
year = "2022",
abstract = "Rosmarinic acid is a polyphenolic compound, abundantly present in herbs of the Lamiaceae family. The aim of
the study was to evaluate the immunomodulatory properties of a recently developed phenethyl ester derivative
of rosmarinic acid (PERA), with enhanced ability of diffusion through biological membranes, in an animal model
of the central nervous system (CNS) autoimmunity. To this end, experimental autoimmune encephalomyelitis
(EAE), an animal model of multiple sclerosis was used. Daily subcutaneous administration of PERA (30 mg/kg)
from day 7 to day 22 after immunization successfully ameliorated EAE induced in Dark Agouti rats, shortening
the disease duration and reducing maximal, cumulative and mean clinical score. PERA efficiently reduced
production of major encephalitogenic cytokines, interferon (IFN)-γ and interleukin (IL)-17, in immune cells from
the CNS or the lymph nodes draining the site of immunization of EAE rats, as well as in CD4+ T cells purified
from the lymph nodes. Also, PERA inhibited NO production in the CNS and the lymph nodes, as well as in
macrophages and microglial cells. Finally, microglial ability to produce pro-inflammatory cytokines IL-6, and
tumor necrosis factor (TNF) were also reduced by PERA. Our results clearly imply that PERA possesses antiencephalitogenic properties. Thus, further studies on the relevance of the observed effects for the therapy of
multiple sclerosis are warranted.",
publisher = "Amsterdam : Elsevier",
journal = "Immunology Letters",
title = "Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis",
volume = "251-252",
doi = "10.1016/j.imlet.2022.09.006",
pages = "9-19"
}

Stegnjaić, G., Lazarević, M., Diamantis, D. A., Nikolovski, N., Jevtić, B., Stanisavljević, S., Dimitrijević, M., Momčilović, M., Tzakos, A. G.,& Miljković, Đ.. (2022). Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis. in Immunology Letters
Amsterdam : Elsevier., 251-252, 9-19.
https://doi.org/10.1016/j.imlet.2022.09.006

Stegnjaić G, Lazarević M, Diamantis DA, Nikolovski N, Jevtić B, Stanisavljević S, Dimitrijević M, Momčilović M, Tzakos AG, Miljković Đ. Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis. in Immunology Letters. 2022;251-252:9-19.
doi:10.1016/j.imlet.2022.09.006 .

Stegnjaić, Goran, Lazarević, Milica, Diamantis, Dimitrois A, Nikolovski, Neda, Jevtić, Bojan, Stanisavljević, Suzana, Dimitrijević, Mirjana, Momčilović, Miljana, Tzakos, Andreas G, Miljković, Đorđe, "Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis" in Immunology Letters, 251-252 (2022):9-19,
https://doi.org/10.1016/j.imlet.2022.09.006 . .

TY  - CONF
AU  - Milićević, Katarina
AU  - Lazarević, Milica
AU  - Momčilović, Miljana
AU  - Todorović, Nataša
AU  - Petković, Branka
AU  - Stojadinović, Gordana
AU  - Nikolić, Ljiljana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5504
AB  - Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system (CNS)
characterized by infiltration of lymphocytes that leads to myelin damage and neurodegeneration.
The complex interaction between CNS-infiltrating immune cells (CNS-IIC) and astrocytes is an
important contributor to the disease progression. Here, we investigate how naïve astrocytes respond
to autoreactive immune cells present in the CNS at different stages of the disease. For this purpose,
CNS-IICs were isolated from the spinal cords of rats with experimental autoimmune
encephalomyelitis at onset, late-onset and the peak of the disease. Naïve astrocytes, isolated from
the spinal cords of wild-type rat pups, responded to brief bath application of CNS-IIC by robust
elevation of intracellular Ca2+ independently of the disease stage. Our data suggest that direct
contact between astrocytes and CNS-IICs induces Ca2+ changes in astrocytes and points to the new
aspect of cell-cell interactions in the propagation of neuroinflammatory response in CNS
autoimmunity.
PB  - Belgrade: Society of Physical Chemists of Serbia
C3  - Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia
T1  - Naïve astrocytes react to CNS-infiltrated immune cells
SP  - 267
EP  - 270
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5504
ER  - 

@conference{
editor = "Čupić, Željko, Anić, Slobodan",
author = "Milićević, Katarina and Lazarević, Milica and Momčilović, Miljana and Todorović, Nataša and Petković, Branka and Stojadinović, Gordana and Nikolić, Ljiljana",
year = "2022",
abstract = "Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system (CNS)
characterized by infiltration of lymphocytes that leads to myelin damage and neurodegeneration.
The complex interaction between CNS-infiltrating immune cells (CNS-IIC) and astrocytes is an
important contributor to the disease progression. Here, we investigate how naïve astrocytes respond
to autoreactive immune cells present in the CNS at different stages of the disease. For this purpose,
CNS-IICs were isolated from the spinal cords of rats with experimental autoimmune
encephalomyelitis at onset, late-onset and the peak of the disease. Naïve astrocytes, isolated from
the spinal cords of wild-type rat pups, responded to brief bath application of CNS-IIC by robust
elevation of intracellular Ca2+ independently of the disease stage. Our data suggest that direct
contact between astrocytes and CNS-IICs induces Ca2+ changes in astrocytes and points to the new
aspect of cell-cell interactions in the propagation of neuroinflammatory response in CNS
autoimmunity.",
publisher = "Belgrade: Society of Physical Chemists of Serbia",
journal = "Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia",
title = "Naïve astrocytes react to CNS-infiltrated immune cells",
pages = "267-270",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5504"
}

Čupić, Ž., Anić, S., Milićević, K., Lazarević, M., Momčilović, M., Todorović, N., Petković, B., Stojadinović, G.,& Nikolić, L.. (2022). Naïve astrocytes react to CNS-infiltrated immune cells. in Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia
Belgrade: Society of Physical Chemists of Serbia., 267-270.
https://hdl.handle.net/21.15107/rcub_ibiss_5504

Čupić Ž, Anić S, Milićević K, Lazarević M, Momčilović M, Todorović N, Petković B, Stojadinović G, Nikolić L. Naïve astrocytes react to CNS-infiltrated immune cells. in Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia. 2022;:267-270.
https://hdl.handle.net/21.15107/rcub_ibiss_5504 .

Čupić, Željko, Anić, Slobodan, Milićević, Katarina, Lazarević, Milica, Momčilović, Miljana, Todorović, Nataša, Petković, Branka, Stojadinović, Gordana, Nikolić, Ljiljana, "Naïve astrocytes react to CNS-infiltrated immune cells" in Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia (2022):267-270,
https://hdl.handle.net/21.15107/rcub_ibiss_5504 .

TY  - JOUR
AU  - Bijelić, Dunja D.
AU  - Milićević, Katarina D.
AU  - Lazarević, Milica
AU  - Miljković, Đorđe
AU  - Bogdanović Pristov, Jelena J.
AU  - Savić, Danijela
AU  - Petković, Branka
AU  - Anđus, Pavle R.
AU  - Momčilović, Miljana
AU  - Nikolić, Ljiljana
PY  - 2020
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/jnr.24699
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32799373
UR  - https://radar.ibiss.bg.ac.rs/123456789/3859
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4006
AB  - Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naïve astrocytes in culture and CNS-infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell-astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca2+ increase in astrocytes by promoting glial release of ATP. ATP propagated Ca2+ elevation through glial purinergic P2X7 receptor activation by the hemichannel-dependent nucleotide release mechanism. Astrocyte Ca2+ increase is specifically triggered by the autoreactive CD4+ T-cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca2+ signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell-astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease.
PB  - John Wiley and Sons Inc.
T2  - Journal of Neuroscience Research
T1  - Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling
IS  - 11
VL  - 98
DO  - 10.1002/jnr.24699
SP  - 2317
EP  - 2332
ER  - 

@article{
author = "Bijelić, Dunja D. and Milićević, Katarina D. and Lazarević, Milica and Miljković, Đorđe and Bogdanović Pristov, Jelena J. and Savić, Danijela and Petković, Branka and Anđus, Pavle R. and Momčilović, Miljana and Nikolić, Ljiljana",
year = "2020",
abstract = "Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naïve astrocytes in culture and CNS-infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell-astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca2+ increase in astrocytes by promoting glial release of ATP. ATP propagated Ca2+ elevation through glial purinergic P2X7 receptor activation by the hemichannel-dependent nucleotide release mechanism. Astrocyte Ca2+ increase is specifically triggered by the autoreactive CD4+ T-cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca2+ signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell-astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease.",
publisher = "John Wiley and Sons Inc.",
journal = "Journal of Neuroscience Research",
title = "Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling",
number = "11",
volume = "98",
doi = "10.1002/jnr.24699",
pages = "2317-2332"
}

Bijelić, D. D., Milićević, K. D., Lazarević, M., Miljković, Đ., Bogdanović Pristov, J. J., Savić, D., Petković, B., Anđus, P. R., Momčilović, M.,& Nikolić, L.. (2020). Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling. in Journal of Neuroscience Research
John Wiley and Sons Inc.., 98(11), 2317-2332.
https://doi.org/10.1002/jnr.24699

Bijelić DD, Milićević KD, Lazarević M, Miljković Đ, Bogdanović Pristov JJ, Savić D, Petković B, Anđus PR, Momčilović M, Nikolić L. Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling. in Journal of Neuroscience Research. 2020;98(11):2317-2332.
doi:10.1002/jnr.24699 .

Bijelić, Dunja D., Milićević, Katarina D., Lazarević, Milica, Miljković, Đorđe, Bogdanović Pristov, Jelena J., Savić, Danijela, Petković, Branka, Anđus, Pavle R., Momčilović, Miljana, Nikolić, Ljiljana, "Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling" in Journal of Neuroscience Research, 98, no. 11 (2020):2317-2332,
https://doi.org/10.1002/jnr.24699 . .

TY  - JOUR
AU  - Bijelić, Dunja D.
AU  - Milićević, Katarina D.
AU  - Lazarević, Milica
AU  - Miljković, Đorđe
AU  - Bogdanović Pristov, Jelena J.
AU  - Savić, Danijela
AU  - Petković, Branka
AU  - Anđus, Pavle R.
AU  - Momčilović, Miljana
AU  - Nikolić, Ljiljana
PY  - 2020
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/jnr.24699
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32799373
UR  - https://radar.ibiss.bg.ac.rs/123456789/3859
AB  - Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naïve astrocytes in culture and CNS-infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell-astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca2+ increase in astrocytes by promoting glial release of ATP. ATP propagated Ca2+ elevation through glial purinergic P2X7 receptor activation by the hemichannel-dependent nucleotide release mechanism. Astrocyte Ca2+ increase is specifically triggered by the autoreactive CD4+ T-cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca2+ signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell-astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease.
PB  - John Wiley and Sons Inc.
T2  - Journal of Neuroscience Research
T1  - Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling
IS  - 11
VL  - 98
DO  - 10.1002/jnr.24699
SP  - 2317
EP  - 2332
ER  - 

@article{
author = "Bijelić, Dunja D. and Milićević, Katarina D. and Lazarević, Milica and Miljković, Đorđe and Bogdanović Pristov, Jelena J. and Savić, Danijela and Petković, Branka and Anđus, Pavle R. and Momčilović, Miljana and Nikolić, Ljiljana",
year = "2020",
abstract = "Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naïve astrocytes in culture and CNS-infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell-astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca2+ increase in astrocytes by promoting glial release of ATP. ATP propagated Ca2+ elevation through glial purinergic P2X7 receptor activation by the hemichannel-dependent nucleotide release mechanism. Astrocyte Ca2+ increase is specifically triggered by the autoreactive CD4+ T-cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca2+ signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell-astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease.",
publisher = "John Wiley and Sons Inc.",
journal = "Journal of Neuroscience Research",
title = "Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling",
number = "11",
volume = "98",
doi = "10.1002/jnr.24699",
pages = "2317-2332"
}

Bijelić, D. D., Milićević, K. D., Lazarević, M., Miljković, Đ., Bogdanović Pristov, J. J., Savić, D., Petković, B., Anđus, P. R., Momčilović, M.,& Nikolić, L.. (2020). Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling. in Journal of Neuroscience Research
John Wiley and Sons Inc.., 98(11), 2317-2332.
https://doi.org/10.1002/jnr.24699

Bijelić DD, Milićević KD, Lazarević M, Miljković Đ, Bogdanović Pristov JJ, Savić D, Petković B, Anđus PR, Momčilović M, Nikolić L. Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling. in Journal of Neuroscience Research. 2020;98(11):2317-2332.
doi:10.1002/jnr.24699 .

Bijelić, Dunja D., Milićević, Katarina D., Lazarević, Milica, Miljković, Đorđe, Bogdanović Pristov, Jelena J., Savić, Danijela, Petković, Branka, Anđus, Pavle R., Momčilović, Miljana, Nikolić, Ljiljana, "Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling" in Journal of Neuroscience Research, 98, no. 11 (2020):2317-2332,
https://doi.org/10.1002/jnr.24699 . .

TY  - CONF
AU  - Milićević, Katarina
AU  - Bijelić, Dunja
AU  - Lazarević, Milica
AU  - Miljković, Đorđe
AU  - Bogdanović Pristov, Jelena
AU  - Petković, Branka
AU  - Anđus, Pavle
AU  - Momčilović, Miljana
AU  - Nikolić, Ljiljana
PY  - 2020
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5514
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
system (CNS), characterized by focal neurodegenerative and demyelinating lesions.
A major contributor to the pathogenic process of MS is the complex interaction
between astrocytes and the CNS-infiltrating immune cells (CNS-IIC). The aim of our
study is to explore how naïve astrocytes respond to the autoreactive immune cells
that invade the CNS. For this reason, CNS-IICs were isolated and purified from
spinal cords of rats with experimental autoimmune encephalomyelitis. Ca2+
dynamics was monitored in Fluo-4 labeled naïve astrocytes, isolated from spinal
cords of wild type rat pups, following brief bath application of CNS-IIC or peripheral
immune cells, with different pharmacological agents. CNS-IICs, and not peripheral
immune cells, induced robust elevation of intracellular Ca2+ in naïve astrocytes. We
demonstrated that this CNS IIC-induced increase in astrocyte Ca2+ does not depend
on the metabotropic glutamate receptors, metabotropic purinergic P2Y1 receptors
or TRPA1 channels. Remarkably, further research showed that Ca2+ elevation in
astrocytes upon exposure to CNS IICs is due to the activation of ionotropic purinergic
P2X7 receptors. Bioluminescence assay showed that immune cell-derived ATP is
not a cause of astrocytic P2X7 receptor activation. In fact, we showed that CNS-IICs
promoted P2X7 receptor activation and increase in cytosolic Ca2+ in astrocytes by
astrocytic hemichannel-dependent ATP release mechanism. Our data suggest that
direct contact between astrocytes and CNS IICs induce ATP-dependent Ca2+
changes in astrocytes and points to the new aspect of cell-cell interactions in
propagation of neuroinflammatory response in CNS autoimmunity.
PB  - Querétaro, México: Instituto de neurobiologia
C3  - Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual
T1  - Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes
SP  - 45
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5514
ER  - 

@conference{
author = "Milićević, Katarina and Bijelić, Dunja and Lazarević, Milica and Miljković, Đorđe and Bogdanović Pristov, Jelena and Petković, Branka and Anđus, Pavle and Momčilović, Miljana and Nikolić, Ljiljana",
year = "2020",
abstract = "Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
system (CNS), characterized by focal neurodegenerative and demyelinating lesions.
A major contributor to the pathogenic process of MS is the complex interaction
between astrocytes and the CNS-infiltrating immune cells (CNS-IIC). The aim of our
study is to explore how naïve astrocytes respond to the autoreactive immune cells
that invade the CNS. For this reason, CNS-IICs were isolated and purified from
spinal cords of rats with experimental autoimmune encephalomyelitis. Ca2+
dynamics was monitored in Fluo-4 labeled naïve astrocytes, isolated from spinal
cords of wild type rat pups, following brief bath application of CNS-IIC or peripheral
immune cells, with different pharmacological agents. CNS-IICs, and not peripheral
immune cells, induced robust elevation of intracellular Ca2+ in naïve astrocytes. We
demonstrated that this CNS IIC-induced increase in astrocyte Ca2+ does not depend
on the metabotropic glutamate receptors, metabotropic purinergic P2Y1 receptors
or TRPA1 channels. Remarkably, further research showed that Ca2+ elevation in
astrocytes upon exposure to CNS IICs is due to the activation of ionotropic purinergic
P2X7 receptors. Bioluminescence assay showed that immune cell-derived ATP is
not a cause of astrocytic P2X7 receptor activation. In fact, we showed that CNS-IICs
promoted P2X7 receptor activation and increase in cytosolic Ca2+ in astrocytes by
astrocytic hemichannel-dependent ATP release mechanism. Our data suggest that
direct contact between astrocytes and CNS IICs induce ATP-dependent Ca2+
changes in astrocytes and points to the new aspect of cell-cell interactions in
propagation of neuroinflammatory response in CNS autoimmunity.",
publisher = "Querétaro, México: Instituto de neurobiologia",
journal = "Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual",
title = "Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes",
pages = "45",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5514"
}

Milićević, K., Bijelić, D., Lazarević, M., Miljković, Đ., Bogdanović Pristov, J., Petković, B., Anđus, P., Momčilović, M.,& Nikolić, L.. (2020). Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes. in Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual
Querétaro, México: Instituto de neurobiologia., 45.
https://hdl.handle.net/21.15107/rcub_ibiss_5514

Milićević K, Bijelić D, Lazarević M, Miljković Đ, Bogdanović Pristov J, Petković B, Anđus P, Momčilović M, Nikolić L. Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes. in Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual. 2020;:45.
https://hdl.handle.net/21.15107/rcub_ibiss_5514 .

Milićević, Katarina, Bijelić, Dunja, Lazarević, Milica, Miljković, Đorđe, Bogdanović Pristov, Jelena, Petković, Branka, Anđus, Pavle, Momčilović, Miljana, Nikolić, Ljiljana, "Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes" in Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual (2020):45,
https://hdl.handle.net/21.15107/rcub_ibiss_5514 .

TY  - JOUR
AU  - Lazarević, Milica
AU  - Battaglia, Giuseppe
AU  - Jevtić, Bojan
AU  - Nikolovski, Neda
AU  - Bruno, Valeria
AU  - Cavalli, Eugenio
AU  - Miljković, Đorđe
AU  - Nicoletti, Ferdinando
AU  - Momčilović, Miljana
AU  - Fagone, Paolo
PY  - 2020
UR  - https://www.mdpi.com/2076-3921/9/7/608
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32664399
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3819
AB  - The aim of this study was to examine the in vitro effects of the slow-releasing H2S donor GYY4137 on the immune cells involved in the pathogenesis of the central nervous system (CNS) autoimmune disease, multiple sclerosis (MS). GYY4137 specifically potentiated TGF-β expression and production in dendritic cells and significantly reduced IFN-γ and IL-17 production in the lymph node and spinal cord T cells obtained from mice immunized with CNS antigens. Both the proportion of FoxP3+ regulatory CD4+ T cells in the lymph node cells, and the percentage of IL-17+ CD4+ T cells in the spinal cord cells were reduced upon culturing with GYY4137. Interestingly, the peripheral blood mononuclear cells obtained from the MS patients had a lower expression of the H2S-producing enzyme, 3-mercaptopyruvate-sulfurtransferase (MPST), in comparison to those obtained from healthy donors. A significant inverse correlation between the expression of MPST and several pro-inflammatory factors was also observed. Further studies on the relevance of the observed results for the pathogenesis and therapy of MS are warranted.
PB  - MDPI AG
T2  - Antioxidants (Basel, Switzerland)
T2  - Antioxidants (Basel, Switzerland)
T1  - Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis.
IS  - 7
VL  - 9
DO  - 10.3390/antiox9070608
SP  - 608
ER  - 

@article{
author = "Lazarević, Milica and Battaglia, Giuseppe and Jevtić, Bojan and Nikolovski, Neda and Bruno, Valeria and Cavalli, Eugenio and Miljković, Đorđe and Nicoletti, Ferdinando and Momčilović, Miljana and Fagone, Paolo",
year = "2020",
abstract = "The aim of this study was to examine the in vitro effects of the slow-releasing H2S donor GYY4137 on the immune cells involved in the pathogenesis of the central nervous system (CNS) autoimmune disease, multiple sclerosis (MS). GYY4137 specifically potentiated TGF-β expression and production in dendritic cells and significantly reduced IFN-γ and IL-17 production in the lymph node and spinal cord T cells obtained from mice immunized with CNS antigens. Both the proportion of FoxP3+ regulatory CD4+ T cells in the lymph node cells, and the percentage of IL-17+ CD4+ T cells in the spinal cord cells were reduced upon culturing with GYY4137. Interestingly, the peripheral blood mononuclear cells obtained from the MS patients had a lower expression of the H2S-producing enzyme, 3-mercaptopyruvate-sulfurtransferase (MPST), in comparison to those obtained from healthy donors. A significant inverse correlation between the expression of MPST and several pro-inflammatory factors was also observed. Further studies on the relevance of the observed results for the pathogenesis and therapy of MS are warranted.",
publisher = "MDPI AG",
journal = "Antioxidants (Basel, Switzerland), Antioxidants (Basel, Switzerland)",
title = "Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis.",
number = "7",
volume = "9",
doi = "10.3390/antiox9070608",
pages = "608"
}

Lazarević, M., Battaglia, G., Jevtić, B., Nikolovski, N., Bruno, V., Cavalli, E., Miljković, Đ., Nicoletti, F., Momčilović, M.,& Fagone, P.. (2020). Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis.. in Antioxidants (Basel, Switzerland)
MDPI AG., 9(7), 608.
https://doi.org/10.3390/antiox9070608

Lazarević M, Battaglia G, Jevtić B, Nikolovski N, Bruno V, Cavalli E, Miljković Đ, Nicoletti F, Momčilović M, Fagone P. Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis.. in Antioxidants (Basel, Switzerland). 2020;9(7):608.
doi:10.3390/antiox9070608 .

Lazarević, Milica, Battaglia, Giuseppe, Jevtić, Bojan, Nikolovski, Neda, Bruno, Valeria, Cavalli, Eugenio, Miljković, Đorđe, Nicoletti, Ferdinando, Momčilović, Miljana, Fagone, Paolo, "Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis." in Antioxidants (Basel, Switzerland), 9, no. 7 (2020):608,
https://doi.org/10.3390/antiox9070608 . .

TY  - JOUR
AU  - Stanisavljević, Suzana
AU  - Čepić, Aleksa
AU  - Bojić, Svetlana
AU  - Veljović, Katarina
AU  - Mihajlović, Sanja
AU  - Nikolovski, Neda
AU  - Jevtić, Bojan
AU  - Momčilović, Miljana
AU  - Lazarević, Milica
AU  - Mostarica Stojković, Marija
AU  - Miljković, Đorđe
AU  - Golić, Nataša
PY  - 2019
UR  - http://www.nature.com/articles/s41598-018-37505-7
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6351648
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3264
AB  - Gut microbiota dysbiosis has been considered the essential element in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Antibiotics were administered orally to Dark Agouti (DA) rats early in their life with the aim of perturbing gut microbiota and investigating the effects of such intervention on the course of EAE. As a result, the diversity of the gut microbiota was reduced under the influence of antibiotics. Mainly, Firmicutes and Actinobacteria were replaced by Proteobacteria and Bacteroidetes, while decreased proportions of Clostridia and Bacilli classes were accompanied by an increase in Gamma-Proteobacteria in antibiotic-treated animals. Interestingly, a notable decrease in the Helicobacteraceae, Spirochaetaceae and Turicibacteriaceae was scored in antibiotic-treated groups. Also, levels of short chain fatty acids were reduced in the faeces of antibiotic-treated rats. Consequently, aggravation of EAE, paralleled with stronger immune response in lymph nodes draining the site of immunization, and increased inflammation within the CNS, were observed in antibiotic-treated DA rats. Thus, the alteration of gut microbiota leads to an escalation of CNS-directed autoimmunity in DA rats. The results of this study indicate that antibiotic use in early life may have subsequent unfavourable effects on the regulation of the immune system.
T2  - Scientific Reports
T1  - Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats.
IS  - 1
VL  - 9
DO  - 10.1038/s41598-018-37505-7
SP  - 918
ER  - 

@article{
author = "Stanisavljević, Suzana and Čepić, Aleksa and Bojić, Svetlana and Veljović, Katarina and Mihajlović, Sanja and Nikolovski, Neda and Jevtić, Bojan and Momčilović, Miljana and Lazarević, Milica and Mostarica Stojković, Marija and Miljković, Đorđe and Golić, Nataša",
year = "2019",
abstract = "Gut microbiota dysbiosis has been considered the essential element in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Antibiotics were administered orally to Dark Agouti (DA) rats early in their life with the aim of perturbing gut microbiota and investigating the effects of such intervention on the course of EAE. As a result, the diversity of the gut microbiota was reduced under the influence of antibiotics. Mainly, Firmicutes and Actinobacteria were replaced by Proteobacteria and Bacteroidetes, while decreased proportions of Clostridia and Bacilli classes were accompanied by an increase in Gamma-Proteobacteria in antibiotic-treated animals. Interestingly, a notable decrease in the Helicobacteraceae, Spirochaetaceae and Turicibacteriaceae was scored in antibiotic-treated groups. Also, levels of short chain fatty acids were reduced in the faeces of antibiotic-treated rats. Consequently, aggravation of EAE, paralleled with stronger immune response in lymph nodes draining the site of immunization, and increased inflammation within the CNS, were observed in antibiotic-treated DA rats. Thus, the alteration of gut microbiota leads to an escalation of CNS-directed autoimmunity in DA rats. The results of this study indicate that antibiotic use in early life may have subsequent unfavourable effects on the regulation of the immune system.",
journal = "Scientific Reports",
title = "Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats.",
number = "1",
volume = "9",
doi = "10.1038/s41598-018-37505-7",
pages = "918"
}

Stanisavljević, S., Čepić, A., Bojić, S., Veljović, K., Mihajlović, S., Nikolovski, N., Jevtić, B., Momčilović, M., Lazarević, M., Mostarica Stojković, M., Miljković, Đ.,& Golić, N.. (2019). Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats.. in Scientific Reports, 9(1), 918.
https://doi.org/10.1038/s41598-018-37505-7

Stanisavljević S, Čepić A, Bojić S, Veljović K, Mihajlović S, Nikolovski N, Jevtić B, Momčilović M, Lazarević M, Mostarica Stojković M, Miljković Đ, Golić N. Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats.. in Scientific Reports. 2019;9(1):918.
doi:10.1038/s41598-018-37505-7 .

Stanisavljević, Suzana, Čepić, Aleksa, Bojić, Svetlana, Veljović, Katarina, Mihajlović, Sanja, Nikolovski, Neda, Jevtić, Bojan, Momčilović, Miljana, Lazarević, Milica, Mostarica Stojković, Marija, Miljković, Đorđe, Golić, Nataša, "Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats." in Scientific Reports, 9, no. 1 (2019):918,
https://doi.org/10.1038/s41598-018-37505-7 . .

TY  - CONF
AU  - Nikolić, Ljiljana
AU  - Bijelić, Dunja
AU  - Lazarević, Milica
AU  - Milićević, Katarina
AU  - Momčilović, Miljana
AU  - Bogdanović Pristov, Jelena
AU  - Petković, Branka
AU  - Anđus, Pavle
AU  - Miljković, Đorđe
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5500
AB  - Aims: Multiple sclerosis (MS) is an in ammatory autoimmune disorder of the central nervous system (CNS). Complex
interactions between in ltrating immune cells (IIC) and resident glial cells of the CNS cause myelin loss and neuronal dysfunction
in MS. Here we aim to understand how naïve astrocytes functionally respond to the IIC invasion of the CNS.
Methods: We measured calcium activity of naïve astrocytes in culture upon application of IIC. An experimental autoimmune
encephalomyelitis (EAE) MS rat model was used to isolate IIC from the spinal cord of animals at the symptomatic stage. Naïve
astrocytes were isolated from the spinal cord of WT rats.
Results: We show that IIC and not the lymph node immune cells evoke vigorous increase in the astrocyte calcium activity.
This IIC-induced calcium response depends on an autocrine activation of the purinergic P2X7 receptors on the naïve astrocytes.
We also show that IIC induce ATP release from astrocytes by a mechanism that involves gap junctions and/or hemichannels
activation and not the vesicular pathway. Our data indicate that ATP release and subsequent increase in the astrocytic calcium
activity mainly depends on the cell-cell contact between naïve astrocytes and IIC.
Conclusions: These results show that naïve astrocytes functionally respond to the IIC by augmented release of ATP. An increase
in ATP release would alter astrocyte-neuron communication and a ect neuronal function in MS.
PB  - Belgrade : Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Astrocyte activity in the central nervous system autoimmunity
SP  - 295
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5500
ER  - 

@conference{
author = "Nikolić, Ljiljana and Bijelić, Dunja and Lazarević, Milica and Milićević, Katarina and Momčilović, Miljana and Bogdanović Pristov, Jelena and Petković, Branka and Anđus, Pavle and Miljković, Đorđe",
year = "2019",
abstract = "Aims: Multiple sclerosis (MS) is an in ammatory autoimmune disorder of the central nervous system (CNS). Complex
interactions between in ltrating immune cells (IIC) and resident glial cells of the CNS cause myelin loss and neuronal dysfunction
in MS. Here we aim to understand how naïve astrocytes functionally respond to the IIC invasion of the CNS.
Methods: We measured calcium activity of naïve astrocytes in culture upon application of IIC. An experimental autoimmune
encephalomyelitis (EAE) MS rat model was used to isolate IIC from the spinal cord of animals at the symptomatic stage. Naïve
astrocytes were isolated from the spinal cord of WT rats.
Results: We show that IIC and not the lymph node immune cells evoke vigorous increase in the astrocyte calcium activity.
This IIC-induced calcium response depends on an autocrine activation of the purinergic P2X7 receptors on the naïve astrocytes.
We also show that IIC induce ATP release from astrocytes by a mechanism that involves gap junctions and/or hemichannels
activation and not the vesicular pathway. Our data indicate that ATP release and subsequent increase in the astrocytic calcium
activity mainly depends on the cell-cell contact between naïve astrocytes and IIC.
Conclusions: These results show that naïve astrocytes functionally respond to the IIC by augmented release of ATP. An increase
in ATP release would alter astrocyte-neuron communication and a ect neuronal function in MS.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Astrocyte activity in the central nervous system autoimmunity",
pages = "295",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5500"
}

Nikolić, L., Bijelić, D., Lazarević, M., Milićević, K., Momčilović, M., Bogdanović Pristov, J., Petković, B., Anđus, P.,& Miljković, Đ.. (2019). Astrocyte activity in the central nervous system autoimmunity. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade : Serbian Neuroscience Society., 295.
https://hdl.handle.net/21.15107/rcub_ibiss_5500

Nikolić L, Bijelić D, Lazarević M, Milićević K, Momčilović M, Bogdanović Pristov J, Petković B, Anđus P, Miljković Đ. Astrocyte activity in the central nervous system autoimmunity. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:295.
https://hdl.handle.net/21.15107/rcub_ibiss_5500 .

Nikolić, Ljiljana, Bijelić, Dunja, Lazarević, Milica, Milićević, Katarina, Momčilović, Miljana, Bogdanović Pristov, Jelena, Petković, Branka, Anđus, Pavle, Miljković, Đorđe, "Astrocyte activity in the central nervous system autoimmunity" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):295,
https://hdl.handle.net/21.15107/rcub_ibiss_5500 .

TY  - JOUR
AU  - Stanisavljević, Suzana
AU  - Dinić, Miroslav
AU  - Jevtić, Bojan
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Đokić, Jelena
AU  - Golić, Nataša
AU  - Mostarica Stojković, Marija
AU  - Miljković, Đorđe
PY  - 2018
UR  - http://journal.frontiersin.org/article/10.3389/fimmu.2018.00942/full
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5942155
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3056
AB  - Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response. Therefore, modulation of AO gut microbiota by antibiotics was performed in this study. The treatment altered composition of gut microbiota in AO rats and led to a reduction in the proportion of regulatory T cells in Peyer's patches, mesenteric lymph nodes, and in lymph nodes draining the site of immunization. Upregulation of interferon-γ and interleukin (IL)-17 production was observed in the draining lymph nodes. The treatment led to clinically manifested EAE in AO rats with more numerous infiltrates and higher production of IL-17 observed in the CNS. Importantly, transfer of AO gut microbiota into EAE-prone Dark Agouti rats ameliorated the disease. These results clearly imply that gut microbiota is an important factor in AO rat resistance to EAE and that gut microbiota transfer is an efficacious way to treat CNS autoimmunity. These findings also support the idea that gut microbiota modulation has a potential as a future treatment of multiple sclerosis.
T2  - Frontiers in Immunology
T1  - Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.
VL  - 9
DO  - 10.3389/fimmu.2018.00942
SP  - 942
ER  - 

@article{
author = "Stanisavljević, Suzana and Dinić, Miroslav and Jevtić, Bojan and Nikolovski, Neda and Momčilović, Miljana and Đokić, Jelena and Golić, Nataša and Mostarica Stojković, Marija and Miljković, Đorđe",
year = "2018",
abstract = "Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response. Therefore, modulation of AO gut microbiota by antibiotics was performed in this study. The treatment altered composition of gut microbiota in AO rats and led to a reduction in the proportion of regulatory T cells in Peyer's patches, mesenteric lymph nodes, and in lymph nodes draining the site of immunization. Upregulation of interferon-γ and interleukin (IL)-17 production was observed in the draining lymph nodes. The treatment led to clinically manifested EAE in AO rats with more numerous infiltrates and higher production of IL-17 observed in the CNS. Importantly, transfer of AO gut microbiota into EAE-prone Dark Agouti rats ameliorated the disease. These results clearly imply that gut microbiota is an important factor in AO rat resistance to EAE and that gut microbiota transfer is an efficacious way to treat CNS autoimmunity. These findings also support the idea that gut microbiota modulation has a potential as a future treatment of multiple sclerosis.",
journal = "Frontiers in Immunology",
title = "Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.",
volume = "9",
doi = "10.3389/fimmu.2018.00942",
pages = "942"
}

Stanisavljević, S., Dinić, M., Jevtić, B., Nikolovski, N., Momčilović, M., Đokić, J., Golić, N., Mostarica Stojković, M.,& Miljković, Đ.. (2018). Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.. in Frontiers in Immunology, 9, 942.
https://doi.org/10.3389/fimmu.2018.00942

Stanisavljević S, Dinić M, Jevtić B, Nikolovski N, Momčilović M, Đokić J, Golić N, Mostarica Stojković M, Miljković Đ. Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.. in Frontiers in Immunology. 2018;9:942.
doi:10.3389/fimmu.2018.00942 .

Stanisavljević, Suzana, Dinić, Miroslav, Jevtić, Bojan, Nikolovski, Neda, Momčilović, Miljana, Đokić, Jelena, Golić, Nataša, Mostarica Stojković, Marija, Miljković, Đorđe, "Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis." in Frontiers in Immunology, 9 (2018):942,
https://doi.org/10.3389/fimmu.2018.00942 . .

TY  - JOUR
AU  - Lazarević, Milica
AU  - Mazzon, Emanuela
AU  - Momčilović, Miljana
AU  - Basile, Maria Sofia
AU  - Colletti, Giuseppe
AU  - Petralia, Maria Cristina
AU  - Bramanti, Placido
AU  - Nicoletti, Ferdinando
AU  - Miljković, Đorđe
PY  - 2018
UR  - http://www.mdpi.com/1420-3049/23/11/2966
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3191
AB  - GYY4137 is a hydrogen sulfide (H₂S) donor that has been shown to act in an anti-inflammatory manner in vitro and in vivo. Microglial cells are among the major players in immunoinflammatory, degenerative, and neoplastic disorders of the central nervous system, including multiple sclerosis, Parkinson's disease, Alzheimer's disease, and glioblastoma multiforme. So far, the effects of GYY4137 on microglial cells have not been thoroughly investigated. In this study, BV2 microglial cells were stimulated with interferon-gamma and lipopolysaccharide and treated with GYY4137. The agent did not influence the viability of BV2 cells in concentrations up to 200 μM. It inhibited tumor necrosis factor but not interleukin-6 production. Expression of CD40 and CD86 were reduced under the influence of the donor. The phagocytic ability of BV2 cells and nitric oxide production were also affected by the agent. Surprisingly, GYY4137 upregulated generation of reactive oxygen species (ROS) by BV2 cells. The effect was mimicked by another H₂S donor, Na₂S, and it was not reproduced in macrophages. Our results demonstrate that GYY4137 downregulates inflammatory properties of BV2 cells but increases their ability to generate ROS. Further investigation of this unexpected phenomenon is warranted.
T2  - Molecules (Basel, Switzerland)
T1  - The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide.
IS  - 11
VL  - 23
DO  - 10.3390/molecules23112966
SP  - 2966
ER  - 

@article{
author = "Lazarević, Milica and Mazzon, Emanuela and Momčilović, Miljana and Basile, Maria Sofia and Colletti, Giuseppe and Petralia, Maria Cristina and Bramanti, Placido and Nicoletti, Ferdinando and Miljković, Đorđe",
year = "2018",
abstract = "GYY4137 is a hydrogen sulfide (H₂S) donor that has been shown to act in an anti-inflammatory manner in vitro and in vivo. Microglial cells are among the major players in immunoinflammatory, degenerative, and neoplastic disorders of the central nervous system, including multiple sclerosis, Parkinson's disease, Alzheimer's disease, and glioblastoma multiforme. So far, the effects of GYY4137 on microglial cells have not been thoroughly investigated. In this study, BV2 microglial cells were stimulated with interferon-gamma and lipopolysaccharide and treated with GYY4137. The agent did not influence the viability of BV2 cells in concentrations up to 200 μM. It inhibited tumor necrosis factor but not interleukin-6 production. Expression of CD40 and CD86 were reduced under the influence of the donor. The phagocytic ability of BV2 cells and nitric oxide production were also affected by the agent. Surprisingly, GYY4137 upregulated generation of reactive oxygen species (ROS) by BV2 cells. The effect was mimicked by another H₂S donor, Na₂S, and it was not reproduced in macrophages. Our results demonstrate that GYY4137 downregulates inflammatory properties of BV2 cells but increases their ability to generate ROS. Further investigation of this unexpected phenomenon is warranted.",
journal = "Molecules (Basel, Switzerland)",
title = "The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide.",
number = "11",
volume = "23",
doi = "10.3390/molecules23112966",
pages = "2966"
}

Lazarević, M., Mazzon, E., Momčilović, M., Basile, M. S., Colletti, G., Petralia, M. C., Bramanti, P., Nicoletti, F.,& Miljković, Đ.. (2018). The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide.. in Molecules (Basel, Switzerland), 23(11), 2966.
https://doi.org/10.3390/molecules23112966

Lazarević M, Mazzon E, Momčilović M, Basile MS, Colletti G, Petralia MC, Bramanti P, Nicoletti F, Miljković Đ. The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide.. in Molecules (Basel, Switzerland). 2018;23(11):2966.
doi:10.3390/molecules23112966 .

Lazarević, Milica, Mazzon, Emanuela, Momčilović, Miljana, Basile, Maria Sofia, Colletti, Giuseppe, Petralia, Maria Cristina, Bramanti, Placido, Nicoletti, Ferdinando, Miljković, Đorđe, "The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide." in Molecules (Basel, Switzerland), 23, no. 11 (2018):2966,
https://doi.org/10.3390/molecules23112966 . .

TY  - JOUR
AU  - Stojanović, Ivana D.
AU  - Šavikin, Katarina
AU  - Nikolovski, Neda
AU  - Živković, Jelena
AU  - Saksida, Tamara
AU  - Momčilović, Miljana
AU  - Koprivica, Ivan
AU  - Vujičić, Milica
AU  - Stanisavljević, Suzana
AU  - Miljković, Đorđe
AU  - Menković, Nebojša
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S1756464617303353
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2793
AB  - Pomegranate peel extract (PPE) was obtained by aqueous-ethanol extraction and was abundant in punicalin, punicalagin and ellagic acid. As these compounds are known to act against inflammation and oxidative stress in synergistic fashion, effects of PPE were tested in vitro on immune cells and in animal models of multiple sclerosis and type 1 diabetes (T1D). In vitro, PPE inhibited interleukin-17 (IL-17) production from gut-associated lymphoid tissue (GALT) cells. PPE also reduced production of IL-17 in activated T cells isolated from animals with experimental autoimmune encephalomyelitis (EAE). It efficiently down-regulated clinical symptoms of EAE in DA rats and of streptozotocin-induced T1D in C57BL/6 mice. The effect of PPE in T1D was mediated by inhibition of immune cell infiltration into pancreatic islets and through interference with IL-17 and IFN-γ production in GALT. Our results suggest that PPE has the potential to be used as phytopharmaceutical for certain autoimmune and chronic inflammatory disorders.
T2  - Journal of Functional Foods
T1  - Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes
VL  - 35
DO  - 10.1016/j.jff.2017.06.021
SP  - 522
EP  - 530
ER  - 

@article{
author = "Stojanović, Ivana D. and Šavikin, Katarina and Nikolovski, Neda and Živković, Jelena and Saksida, Tamara and Momčilović, Miljana and Koprivica, Ivan and Vujičić, Milica and Stanisavljević, Suzana and Miljković, Đorđe and Menković, Nebojša",
year = "2017",
abstract = "Pomegranate peel extract (PPE) was obtained by aqueous-ethanol extraction and was abundant in punicalin, punicalagin and ellagic acid. As these compounds are known to act against inflammation and oxidative stress in synergistic fashion, effects of PPE were tested in vitro on immune cells and in animal models of multiple sclerosis and type 1 diabetes (T1D). In vitro, PPE inhibited interleukin-17 (IL-17) production from gut-associated lymphoid tissue (GALT) cells. PPE also reduced production of IL-17 in activated T cells isolated from animals with experimental autoimmune encephalomyelitis (EAE). It efficiently down-regulated clinical symptoms of EAE in DA rats and of streptozotocin-induced T1D in C57BL/6 mice. The effect of PPE in T1D was mediated by inhibition of immune cell infiltration into pancreatic islets and through interference with IL-17 and IFN-γ production in GALT. Our results suggest that PPE has the potential to be used as phytopharmaceutical for certain autoimmune and chronic inflammatory disorders.",
journal = "Journal of Functional Foods",
title = "Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes",
volume = "35",
doi = "10.1016/j.jff.2017.06.021",
pages = "522-530"
}

Stojanović, I. D., Šavikin, K., Nikolovski, N., Živković, J., Saksida, T., Momčilović, M., Koprivica, I., Vujičić, M., Stanisavljević, S., Miljković, Đ.,& Menković, N.. (2017). Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes. in Journal of Functional Foods, 35, 522-530.
https://doi.org/10.1016/j.jff.2017.06.021

Stojanović ID, Šavikin K, Nikolovski N, Živković J, Saksida T, Momčilović M, Koprivica I, Vujičić M, Stanisavljević S, Miljković Đ, Menković N. Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes. in Journal of Functional Foods. 2017;35:522-530.
doi:10.1016/j.jff.2017.06.021 .

Stojanović, Ivana D., Šavikin, Katarina, Nikolovski, Neda, Živković, Jelena, Saksida, Tamara, Momčilović, Miljana, Koprivica, Ivan, Vujičić, Milica, Stanisavljević, Suzana, Miljković, Đorđe, Menković, Nebojša, "Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes" in Journal of Functional Foods, 35 (2017):522-530,
https://doi.org/10.1016/j.jff.2017.06.021 . .

TY  - JOUR
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Vujičić, Milica
AU  - Saksida, Tamara
AU  - Jevtić, Bojan
AU  - Milovanović, Boško
AU  - Momčilović, Miljana
AU  - Miljković, Đorđe
AU  - Stojanović, Ivana D.
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0165247817301979
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2854
AB  - C57BL/6, BALB/c and NOD mice are among the most frequently used strains in autoimmunity research. NOD mice spontaneously develop type 1 diabetes (T1D) and they are prone to induction of experimental autoimmune encephalomyelitis (EAE). Both diseases can be routinely induced in C57BL/6 mice, but not in BALB/c mice. Also, C57BL/6 mice are generally considered T helper (Th)1-biased and BALB/c Th2-biased mice. Having in mind increasingly appreciated role of gut associated lymphoid tissue (GALT) cells in autoimmunity, especially in relation to gut Th17 and regulatory T (Treg) cells, our aim was to determine if there are differences in proportion of CD4 + T cell populations in mesenteric lymph nodes and Peyer's p atches of these mouse strains. Lower proportion of Treg was observed in NOD PP, Th2 cells dominated in BALB/c mice in mesenteric lymph nodes (MLN) and Peyer's patches (PP), while Th1 cells prevailed in C57BL/6 MLN. Intradermal immunization of mice with complete Freund's adjuvant resulted in significant difference in Th cell distribution in GALT of NOD mice. Differences were less pronounced in C57BL/6 mice, while GALT of BALB/c mice was almost unresponsive to the immunization. The observed strain- and tissue-dependent changes in Treg proportion after the immunization was probably a consequence of different CCR2 or CCR6-related migration patterns and/or in situ Treg proliferation. In conclusion, NOD, a highly autoimmunity-prone mouse strain, exhibits more profound GALT-related immune response upon immunization compared to the strains that are less prone to autoimmunity.
T2  - Immunology Letters
T1  - Strain-specific helper T cell profile in the gut-associated lymphoid tissue
VL  - 190
DO  - 10.1016/j.imlet.2017.08.017
SP  - 282
EP  - 288
ER  - 

@article{
author = "Stanisavljević, Suzana and Nikolovski, Neda and Vujičić, Milica and Saksida, Tamara and Jevtić, Bojan and Milovanović, Boško and Momčilović, Miljana and Miljković, Đorđe and Stojanović, Ivana D.",
year = "2017",
abstract = "C57BL/6, BALB/c and NOD mice are among the most frequently used strains in autoimmunity research. NOD mice spontaneously develop type 1 diabetes (T1D) and they are prone to induction of experimental autoimmune encephalomyelitis (EAE). Both diseases can be routinely induced in C57BL/6 mice, but not in BALB/c mice. Also, C57BL/6 mice are generally considered T helper (Th)1-biased and BALB/c Th2-biased mice. Having in mind increasingly appreciated role of gut associated lymphoid tissue (GALT) cells in autoimmunity, especially in relation to gut Th17 and regulatory T (Treg) cells, our aim was to determine if there are differences in proportion of CD4 + T cell populations in mesenteric lymph nodes and Peyer's p atches of these mouse strains. Lower proportion of Treg was observed in NOD PP, Th2 cells dominated in BALB/c mice in mesenteric lymph nodes (MLN) and Peyer's patches (PP), while Th1 cells prevailed in C57BL/6 MLN. Intradermal immunization of mice with complete Freund's adjuvant resulted in significant difference in Th cell distribution in GALT of NOD mice. Differences were less pronounced in C57BL/6 mice, while GALT of BALB/c mice was almost unresponsive to the immunization. The observed strain- and tissue-dependent changes in Treg proportion after the immunization was probably a consequence of different CCR2 or CCR6-related migration patterns and/or in situ Treg proliferation. In conclusion, NOD, a highly autoimmunity-prone mouse strain, exhibits more profound GALT-related immune response upon immunization compared to the strains that are less prone to autoimmunity.",
journal = "Immunology Letters",
title = "Strain-specific helper T cell profile in the gut-associated lymphoid tissue",
volume = "190",
doi = "10.1016/j.imlet.2017.08.017",
pages = "282-288"
}

Stanisavljević, S., Nikolovski, N., Vujičić, M., Saksida, T., Jevtić, B., Milovanović, B., Momčilović, M., Miljković, Đ.,& Stojanović, I. D.. (2017). Strain-specific helper T cell profile in the gut-associated lymphoid tissue. in Immunology Letters, 190, 282-288.
https://doi.org/10.1016/j.imlet.2017.08.017

Stanisavljević S, Nikolovski N, Vujičić M, Saksida T, Jevtić B, Milovanović B, Momčilović M, Miljković Đ, Stojanović ID. Strain-specific helper T cell profile in the gut-associated lymphoid tissue. in Immunology Letters. 2017;190:282-288.
doi:10.1016/j.imlet.2017.08.017 .

Stanisavljević, Suzana, Nikolovski, Neda, Vujičić, Milica, Saksida, Tamara, Jevtić, Bojan, Milovanović, Boško, Momčilović, Miljana, Miljković, Đorđe, Stojanović, Ivana D., "Strain-specific helper T cell profile in the gut-associated lymphoid tissue" in Immunology Letters, 190 (2017):282-288,
https://doi.org/10.1016/j.imlet.2017.08.017 . .

TY  - JOUR
AU  - Nikolovski, Neda
AU  - Stanisavljević, Suzana
AU  - Jevtić, Bojan
AU  - Momčilović, Miljana
AU  - Lavrnja, Irena
AU  - Miljković, Đorđe
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0753332217331694
UR  - http://www.sciencedirect.com/science/article/pii/S0753332217331694
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2864
AB  - Ethyl pyruvate is a redox analogue of dimethyl fumarate (Tecfidera), a drug for multiple sclerosis treatment. We have recently shown that ethyl pyruvate ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. It affects encephalitogenic T cells and macrophages in vitro, as well as in lymph nodes draining the site of encephalitogenic immunization and within the central nervous system (CNS). Here, in vivo effects of ethyl pyruvate on EAE are thoroughly investigated in the CNS and within the gut associated lymphoid tissue. Ethyl pyruvate reduced infiltrates within the CNS and number of activated macrophages/microglia (ED1(+)/Iba1(+)) and proliferating astrocytes (GFAP(+)). Furthermore, it reduced expression of HMGB1 in activated macrophages/microglia. It also reduced number of activated T cells and antigen-presenting cells and expression of Th1/Th17-related molecules in mesenteric lymph nodes and Peyer's patches. These results contribute to our understanding of anti-encephalitogenic effects of ethyl pyruvate as they provide evidence of its effects within the CNS and imply that these effects are related to reduction of inflammatory immune response in gut associated lymphoid tissue.
T2  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
T1  - Anti-encephalitogenic effects of ethyl pyruvate are reflected in the central nervous system and the gut.
VL  - 96
DO  - 10.1016/j.biopha.2017.09.110
SP  - 78
EP  - 85
ER  - 

@article{
author = "Nikolovski, Neda and Stanisavljević, Suzana and Jevtić, Bojan and Momčilović, Miljana and Lavrnja, Irena and Miljković, Đorđe",
year = "2017",
abstract = "Ethyl pyruvate is a redox analogue of dimethyl fumarate (Tecfidera), a drug for multiple sclerosis treatment. We have recently shown that ethyl pyruvate ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. It affects encephalitogenic T cells and macrophages in vitro, as well as in lymph nodes draining the site of encephalitogenic immunization and within the central nervous system (CNS). Here, in vivo effects of ethyl pyruvate on EAE are thoroughly investigated in the CNS and within the gut associated lymphoid tissue. Ethyl pyruvate reduced infiltrates within the CNS and number of activated macrophages/microglia (ED1(+)/Iba1(+)) and proliferating astrocytes (GFAP(+)). Furthermore, it reduced expression of HMGB1 in activated macrophages/microglia. It also reduced number of activated T cells and antigen-presenting cells and expression of Th1/Th17-related molecules in mesenteric lymph nodes and Peyer's patches. These results contribute to our understanding of anti-encephalitogenic effects of ethyl pyruvate as they provide evidence of its effects within the CNS and imply that these effects are related to reduction of inflammatory immune response in gut associated lymphoid tissue.",
journal = "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie",
title = "Anti-encephalitogenic effects of ethyl pyruvate are reflected in the central nervous system and the gut.",
volume = "96",
doi = "10.1016/j.biopha.2017.09.110",
pages = "78-85"
}

Nikolovski, N., Stanisavljević, S., Jevtić, B., Momčilović, M., Lavrnja, I.,& Miljković, Đ.. (2017). Anti-encephalitogenic effects of ethyl pyruvate are reflected in the central nervous system and the gut.. in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 96, 78-85.
https://doi.org/10.1016/j.biopha.2017.09.110

Nikolovski N, Stanisavljević S, Jevtić B, Momčilović M, Lavrnja I, Miljković Đ. Anti-encephalitogenic effects of ethyl pyruvate are reflected in the central nervous system and the gut.. in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2017;96:78-85.
doi:10.1016/j.biopha.2017.09.110 .

Nikolovski, Neda, Stanisavljević, Suzana, Jevtić, Bojan, Momčilović, Miljana, Lavrnja, Irena, Miljković, Đorđe, "Anti-encephalitogenic effects of ethyl pyruvate are reflected in the central nervous system and the gut." in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 96 (2017):78-85,
https://doi.org/10.1016/j.biopha.2017.09.110 . .

TY  - JOUR
AU  - Momčilović, Miljana
AU  - Stamenković, Vera
AU  - Jovanović, Miloš
AU  - Anđus, Pavle R.
AU  - Jakovčevski, Igor
AU  - Schachner, Melitta
AU  - Miljković, Đorđe
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0165572816302077
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2497
AB  - The extracellular matrix glycoprotein tenascin-C (TnC) has been increasingly appreciated as a molecule susceptibly reacting to abnormalities in the mammalian immune system. TnC expression is elevated in inflamed tissues outside the immune system, but also in lymphoid organs. It participates in the promotion of inflammatory responses. Here, the role of TnC in a paradigm of CNS autoimmunity was investigated. Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, was induced in mice deficient in TnC (TnC−/− mice). Amelioration of EAE was observed in these mice in comparison to their wild-type (TnC+/+) littermates. Since T helper (Th)1 and Th17 cells play a dominant role in the pathogenesis of EAE, these cells were investigated in addition to analyzing locomotor functions and pro-inflammatory cytokine levels. Smaller numbers of interferon-gamma-producing Th1 cells and reduced ability of Th17 cells to produce interleukin-17 were observed in spleens of TnC−/− mice challenged by immunization with the myelin associated glycoprotein (MOG) when compared to TnC+/+ mice. There was no difference in Th1 and Th17 responses in non-immunized TnC−/− and TnC+/+ mice, thus excluding generalized immunosuppression in TnC−/− mice. These results show that TnC is important for the pathogenesis of CNS autoimmunity and that its deficiency interferes with Th1 and Th17 encephalitogenic potentials.
T2  - Journal of Neuroimmunology
T1  - Tenascin-C deficiency protects mice from experimental autoimmune encephalomyelitis
VL  - 302
DO  - 10.1016/j.jneuroim.2016.12.001
SP  - 1
EP  - 6
ER  - 

@article{
author = "Momčilović, Miljana and Stamenković, Vera and Jovanović, Miloš and Anđus, Pavle R. and Jakovčevski, Igor and Schachner, Melitta and Miljković, Đorđe",
year = "2017",
abstract = "The extracellular matrix glycoprotein tenascin-C (TnC) has been increasingly appreciated as a molecule susceptibly reacting to abnormalities in the mammalian immune system. TnC expression is elevated in inflamed tissues outside the immune system, but also in lymphoid organs. It participates in the promotion of inflammatory responses. Here, the role of TnC in a paradigm of CNS autoimmunity was investigated. Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, was induced in mice deficient in TnC (TnC−/− mice). Amelioration of EAE was observed in these mice in comparison to their wild-type (TnC+/+) littermates. Since T helper (Th)1 and Th17 cells play a dominant role in the pathogenesis of EAE, these cells were investigated in addition to analyzing locomotor functions and pro-inflammatory cytokine levels. Smaller numbers of interferon-gamma-producing Th1 cells and reduced ability of Th17 cells to produce interleukin-17 were observed in spleens of TnC−/− mice challenged by immunization with the myelin associated glycoprotein (MOG) when compared to TnC+/+ mice. There was no difference in Th1 and Th17 responses in non-immunized TnC−/− and TnC+/+ mice, thus excluding generalized immunosuppression in TnC−/− mice. These results show that TnC is important for the pathogenesis of CNS autoimmunity and that its deficiency interferes with Th1 and Th17 encephalitogenic potentials.",
journal = "Journal of Neuroimmunology",
title = "Tenascin-C deficiency protects mice from experimental autoimmune encephalomyelitis",
volume = "302",
doi = "10.1016/j.jneuroim.2016.12.001",
pages = "1-6"
}

Momčilović, M., Stamenković, V., Jovanović, M., Anđus, P. R., Jakovčevski, I., Schachner, M.,& Miljković, Đ.. (2017). Tenascin-C deficiency protects mice from experimental autoimmune encephalomyelitis. in Journal of Neuroimmunology, 302, 1-6.
https://doi.org/10.1016/j.jneuroim.2016.12.001

Momčilović M, Stamenković V, Jovanović M, Anđus PR, Jakovčevski I, Schachner M, Miljković Đ. Tenascin-C deficiency protects mice from experimental autoimmune encephalomyelitis. in Journal of Neuroimmunology. 2017;302:1-6.
doi:10.1016/j.jneuroim.2016.12.001 .

Momčilović, Miljana, Stamenković, Vera, Jovanović, Miloš, Anđus, Pavle R., Jakovčevski, Igor, Schachner, Melitta, Miljković, Đorđe, "Tenascin-C deficiency protects mice from experimental autoimmune encephalomyelitis" in Journal of Neuroimmunology, 302 (2017):1-6,
https://doi.org/10.1016/j.jneuroim.2016.12.001 . .

TY  - JOUR
AU  - Stanisavljević, Suzana
AU  - Lukić, Jovanka
AU  - Momčilović, Miljana
AU  - Miljković, Marija
AU  - Jevtić, Bojan
AU  - Kojić, Milan
AU  - Golić, Nataša
AU  - Mostarica Stojković, Marija
AU  - Miljković, Đorđe
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6049
AB  - Gut microbiota and gut-associated lymphoid tissue have been increasingly appreciated as important players in pathogenesis of various autoimmune diseases, including multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that can be induced with an injection of spinal cord homogenate emulsified in complete Freund's adjuvant in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats. In this study, mesenteric lymph nodes (MLN), Peyer's patches (PP) and gut microbiota were analysed in these two rat strains. There was higher proportion of CD4(+) T cells and regulatory T cells in non-immunised DA rats in comparison to AO rats. Also, DA rat MLN and PP cells were higher producers of pro-inflammatory cytokines interferon-γ and interleukin-17. Finally, microbial analyses showed that uncultivated species of Turicibacter and Atopostipes genus were exclusively present in AO rats, in faeces and intestinal tissue, respectively. Thus, it is clear that in comparison of an EAE-susceptible with an EAE-resistant strain of rats, various discrepancies at the level of gut associated lymphoid tissue, as well as at the level of gut microbiota can be observed. Future studies should determine if the differences have functional significance for EAE pathogenesis.
PB  - Wageningen Academic Publishers
T2  - Beneficial Microbes
T1  - Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis
IS  - 3
VL  - 7
DO  - 10.3920/BM2015.0159
SP  - 363
EP  - 373
ER  - 

@article{
author = "Stanisavljević, Suzana and Lukić, Jovanka and Momčilović, Miljana and Miljković, Marija and Jevtić, Bojan and Kojić, Milan and Golić, Nataša and Mostarica Stojković, Marija and Miljković, Đorđe",
year = "2016",
abstract = "Gut microbiota and gut-associated lymphoid tissue have been increasingly appreciated as important players in pathogenesis of various autoimmune diseases, including multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that can be induced with an injection of spinal cord homogenate emulsified in complete Freund's adjuvant in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats. In this study, mesenteric lymph nodes (MLN), Peyer's patches (PP) and gut microbiota were analysed in these two rat strains. There was higher proportion of CD4(+) T cells and regulatory T cells in non-immunised DA rats in comparison to AO rats. Also, DA rat MLN and PP cells were higher producers of pro-inflammatory cytokines interferon-γ and interleukin-17. Finally, microbial analyses showed that uncultivated species of Turicibacter and Atopostipes genus were exclusively present in AO rats, in faeces and intestinal tissue, respectively. Thus, it is clear that in comparison of an EAE-susceptible with an EAE-resistant strain of rats, various discrepancies at the level of gut associated lymphoid tissue, as well as at the level of gut microbiota can be observed. Future studies should determine if the differences have functional significance for EAE pathogenesis.",
publisher = "Wageningen Academic Publishers",
journal = "Beneficial Microbes",
title = "Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis",
number = "3",
volume = "7",
doi = "10.3920/BM2015.0159",
pages = "363-373"
}

Stanisavljević, S., Lukić, J., Momčilović, M., Miljković, M., Jevtić, B., Kojić, M., Golić, N., Mostarica Stojković, M.,& Miljković, Đ.. (2016). Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis. in Beneficial Microbes
Wageningen Academic Publishers., 7(3), 363-373.
https://doi.org/10.3920/BM2015.0159

Stanisavljević S, Lukić J, Momčilović M, Miljković M, Jevtić B, Kojić M, Golić N, Mostarica Stojković M, Miljković Đ. Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis. in Beneficial Microbes. 2016;7(3):363-373.
doi:10.3920/BM2015.0159 .

Stanisavljević, Suzana, Lukić, Jovanka, Momčilović, Miljana, Miljković, Marija, Jevtić, Bojan, Kojić, Milan, Golić, Nataša, Mostarica Stojković, Marija, Miljković, Đorđe, "Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis" in Beneficial Microbes, 7, no. 3 (2016):363-373,
https://doi.org/10.3920/BM2015.0159 . .