TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Marinho, Sergio
AU  - Moura-Alves, Pedro
AU  - Pavić, Aleksandar
AU  - Otašević, Vesna
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6296
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that has an important role in regulating the immune system, with high expression in Th17 CD4+ T cells and T regulatory cells (Treg). The expression of AhR is especially important at mucosal surfaces where it is involved in balancing the immune response towards external factors. The aim of our research was to evaluate the effect on the gut immune system of a novel fluorescent indole-containing compound that was designed as a putative AhR ligand (encoded C43). By using the EROD assay, we determined that C43 has mild AhR agonistic activity. Sort-purified mesenteric lymph node (MLN) CD4+ cells were treated with C43 for 24 h and flow cytometry analysis (FCM) showed that the Treg/Th17 ratio shifted in favour of Tregs. Zebrafish embryos were used for the evaluation of potential C43 toxicity. No nephrotoxicity, hepatotoxicity or cardiotoxicity was detected, even at the highest concentrations. Next, C43 was orally administered to healthy male C57BL/6 mice for 5 consecutive days, and later its effects on the gut immune system were recorded by analyzing the MLNs. FCM unveiled a higher proportion of Treg cells that expressed CYP1A1 (downstream effector of AhR) and the ratio of Treg/Th1 shifted towards Tregs. The presence of C43 was also visualized by confocal microscopy in the small intestine lamina propria of treated animals. With such results obtained from healthy animals, C43 presents a promising compound for the treatment of inflammatory diseases that generally involve activation of the gut immune system.
PB  - European Federation of Immunological Societies (EFIS)
C3  - Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia
T1  - Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity
SP  - 17
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6296
ER  - 

@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Marinho, Sergio and Moura-Alves, Pedro and Pavić, Aleksandar and Otašević, Vesna and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2023",
abstract = "The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that has an important role in regulating the immune system, with high expression in Th17 CD4+ T cells and T regulatory cells (Treg). The expression of AhR is especially important at mucosal surfaces where it is involved in balancing the immune response towards external factors. The aim of our research was to evaluate the effect on the gut immune system of a novel fluorescent indole-containing compound that was designed as a putative AhR ligand (encoded C43). By using the EROD assay, we determined that C43 has mild AhR agonistic activity. Sort-purified mesenteric lymph node (MLN) CD4+ cells were treated with C43 for 24 h and flow cytometry analysis (FCM) showed that the Treg/Th17 ratio shifted in favour of Tregs. Zebrafish embryos were used for the evaluation of potential C43 toxicity. No nephrotoxicity, hepatotoxicity or cardiotoxicity was detected, even at the highest concentrations. Next, C43 was orally administered to healthy male C57BL/6 mice for 5 consecutive days, and later its effects on the gut immune system were recorded by analyzing the MLNs. FCM unveiled a higher proportion of Treg cells that expressed CYP1A1 (downstream effector of AhR) and the ratio of Treg/Th1 shifted towards Tregs. The presence of C43 was also visualized by confocal microscopy in the small intestine lamina propria of treated animals. With such results obtained from healthy animals, C43 presents a promising compound for the treatment of inflammatory diseases that generally involve activation of the gut immune system.",
publisher = "European Federation of Immunological Societies (EFIS)",
journal = "Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia",
title = "Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity",
pages = "17",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6296"
}

Jonić, N., Chatzigiannis, C. M., Koprivica, I., Marinho, S., Moura-Alves, P., Pavić, A., Otašević, V., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2023). Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity. in Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia
European Federation of Immunological Societies (EFIS)., 17.
https://hdl.handle.net/21.15107/rcub_ibiss_6296

Jonić N, Chatzigiannis CM, Koprivica I, Marinho S, Moura-Alves P, Pavić A, Otašević V, Pejnović N, Tzakos A, Stojanović ID. Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity. in Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia. 2023;:17.
https://hdl.handle.net/21.15107/rcub_ibiss_6296 .

Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Marinho, Sergio, Moura-Alves, Pedro, Pavić, Aleksandar, Otašević, Vesna, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity" in Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia (2023):17,
https://hdl.handle.net/21.15107/rcub_ibiss_6296 .

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  - Lazarević, Milica
AU  - Stegnjaić, Goran
AU  - Diamantis, Dimitris
AU  - Papaemmanouil, Christina
AU  - Nikolovski, Neda
AU  - Jevtić, Bojan
AU  - Tzakos, Andreas G
AU  - Miljković, Đorđe
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6297
AB  - Rosmarinic acid is a polyphenolic compound, abundantly presentin herbs of the Lamiaceae
family. The aim of the study was to evaluate a recently developed rosmarinic acid
derivative (RAd), with an enhanced ability of diffusion through biological membranes 1, in
preclinical settingsof the central nervous system autoimmunity. To this extent,
experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis
was used. EAE was induced in DA rats by subcutaneous injection of autologous spinal
cord homogenate 2, while treatment with RAd (30 mg/kg) started at 7 day post
immunization and lasted for 15 days. Subcutaneous RAd administration successfully
ameliorated EAE, leading to abbreviation of the disease duration and reducement of
maximal, cumulative and meanclinical score. Also, RAd effects on draining lymph node
cells (DLNC) isolated in the inductive phase of EAE and spinal cord immune cells (SCIC)
obtained at the peak of the diseasewere evaluated. In vitro treatment with RAd (5 μM)
reduced production of major encephalitogenic cytokines, i.e.interferon (IFN)-γ and
interleukin (IL)-17, both in DLNC and SCIC. The reduction of IFN-γ and IL-17
production under the influence of RAd was also detected in the CD4+ T cells purified
fromDLNC, thus suggesting that RAd had a direct effect on CD4+ T cells. Additionally,
the effects of in vitro treatment with RAd were examinedon macrophages (Mf), immune
cells with important role in EAE pathogenesis. Treatment of peritoneal Mf,obtained from
non-immunized DA rats, with RAd (25 μM) led to reduction of NO and IL-6 production,
exterted no effect on IL-1beta production, and elevated tumor necrosis factor production in
Mf. Expression of MHC II and co-stimulatory molecule CD80, the phagocytic ability and
the production of reactive oxygen species in RAd-treated Mf were also downregulated.
Our results imply that RAd possesses anti-inflammatory and antiencephalitogenicproperties. Thus, further studies on the mechanisms behind the observed
effects and their relevance for the therapy of multiple sclerosis are warranted.
PB  - Belgrade: Faculty of Chemistry
C3  - Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
T1  - The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats
SP  - 79
EP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6297
ER  - 

@conference{
author = "Lazarević, Milica and Stegnjaić, Goran and Diamantis, Dimitris and Papaemmanouil, Christina and Nikolovski, Neda and Jevtić, Bojan and Tzakos, Andreas G and Miljković, Đorđe",
year = "2021",
abstract = "Rosmarinic acid is a polyphenolic compound, abundantly presentin herbs of the Lamiaceae
family. The aim of the study was to evaluate a recently developed rosmarinic acid
derivative (RAd), with an enhanced ability of diffusion through biological membranes 1, in
preclinical settingsof the central nervous system autoimmunity. To this extent,
experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis
was used. EAE was induced in DA rats by subcutaneous injection of autologous spinal
cord homogenate 2, while treatment with RAd (30 mg/kg) started at 7 day post
immunization and lasted for 15 days. Subcutaneous RAd administration successfully
ameliorated EAE, leading to abbreviation of the disease duration and reducement of
maximal, cumulative and meanclinical score. Also, RAd effects on draining lymph node
cells (DLNC) isolated in the inductive phase of EAE and spinal cord immune cells (SCIC)
obtained at the peak of the diseasewere evaluated. In vitro treatment with RAd (5 μM)
reduced production of major encephalitogenic cytokines, i.e.interferon (IFN)-γ and
interleukin (IL)-17, both in DLNC and SCIC. The reduction of IFN-γ and IL-17
production under the influence of RAd was also detected in the CD4+ T cells purified
fromDLNC, thus suggesting that RAd had a direct effect on CD4+ T cells. Additionally,
the effects of in vitro treatment with RAd were examinedon macrophages (Mf), immune
cells with important role in EAE pathogenesis. Treatment of peritoneal Mf,obtained from
non-immunized DA rats, with RAd (25 μM) led to reduction of NO and IL-6 production,
exterted no effect on IL-1beta production, and elevated tumor necrosis factor production in
Mf. Expression of MHC II and co-stimulatory molecule CD80, the phagocytic ability and
the production of reactive oxygen species in RAd-treated Mf were also downregulated.
Our results imply that RAd possesses anti-inflammatory and antiencephalitogenicproperties. Thus, further studies on the mechanisms behind the observed
effects and their relevance for the therapy of multiple sclerosis are warranted.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia",
title = "The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats",
pages = "79-80",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6297"
}

Lazarević, M., Stegnjaić, G., Diamantis, D., Papaemmanouil, C., Nikolovski, N., Jevtić, B., Tzakos, A. G.,& Miljković, Đ.. (2021). The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
Belgrade: Faculty of Chemistry., 79-80.
https://hdl.handle.net/21.15107/rcub_ibiss_6297

Lazarević M, Stegnjaić G, Diamantis D, Papaemmanouil C, Nikolovski N, Jevtić B, Tzakos AG, Miljković Đ. The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia. 2021;:79-80.
https://hdl.handle.net/21.15107/rcub_ibiss_6297 .

Lazarević, Milica, Stegnjaić, Goran, Diamantis, Dimitris, Papaemmanouil, Christina, Nikolovski, Neda, Jevtić, Bojan, Tzakos, Andreas G, Miljković, Đorđe, "The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats" in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia (2021):79-80,
https://hdl.handle.net/21.15107/rcub_ibiss_6297 .