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  - 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 . .