TY  - JOUR
AU  - Miljković, Đorđe
AU  - Samardzić, Tatjana
AU  - Drakulić, Danijela
AU  - Stošić-Grujičić, Stanislava
AU  - Trajković, Vladimir
PY  - 2002
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6000
AB  - Mycophenolic acid (MPA) and A77 1726, the active components of the immunosuppressants mycophenolate mophetil and leflunomide, respectively, in a dose-dependent manner inhibited interferon (IFN)-gamma/LPS-induced interleukin (IL)-6 release in confluent cultures of mouse L929 fibrosarcoma cells. In addition, both drugs markedly reduced the production of the free radical gas nitric oxide (NO), without affecting the viability of L929 cells. The inhibitors of NO synthase, aminoguanidine and L-NMMA, but not L-NMMA inactive counterpart D-NMMA, mimicked the effects of A77 1726 and MPA on IL-6 generation in L929 fibroblasts. Furthermore, NO-releasing substance SNP completely reverted IL-6 accumulation in L929 cultures treated with A77 1726, while only partial recovery of IL-6 production was observed in the presence of MPA. MPA, but not A77 1726, significantly suppressed NO-independent IL-6 release triggered by cAMP-elevating agent rolipram. Thus, while A77 1726 effect on IL-6 production was mediated through concomitant reduction of NO synthesis, MPA action was mainly independent of the interference with NO generation. Finally, both agents inhibited IFN-gamma/LPS-triggered IL-6 production in mouse primary fibroblasts, but not in mouse peritoneal macrophages, indicating cell-specificity of this novel anti-inflammatory action of A77 1726 and MPA.
PB  - Elsevier
T2  - Cytokine
T1  - Immunosuppressants leflunomide and mycophenolic acid inhibit fibroblast IL-6 production by distinct mechanisms
IS  - 4
VL  - 19
DO  - 10.1006/cyto.2002.0885
SP  - 181
EP  - 186
ER  - 

@article{
author = "Miljković, Đorđe and Samardzić, Tatjana and Drakulić, Danijela and Stošić-Grujičić, Stanislava and Trajković, Vladimir",
year = "2002",
abstract = "Mycophenolic acid (MPA) and A77 1726, the active components of the immunosuppressants mycophenolate mophetil and leflunomide, respectively, in a dose-dependent manner inhibited interferon (IFN)-gamma/LPS-induced interleukin (IL)-6 release in confluent cultures of mouse L929 fibrosarcoma cells. In addition, both drugs markedly reduced the production of the free radical gas nitric oxide (NO), without affecting the viability of L929 cells. The inhibitors of NO synthase, aminoguanidine and L-NMMA, but not L-NMMA inactive counterpart D-NMMA, mimicked the effects of A77 1726 and MPA on IL-6 generation in L929 fibroblasts. Furthermore, NO-releasing substance SNP completely reverted IL-6 accumulation in L929 cultures treated with A77 1726, while only partial recovery of IL-6 production was observed in the presence of MPA. MPA, but not A77 1726, significantly suppressed NO-independent IL-6 release triggered by cAMP-elevating agent rolipram. Thus, while A77 1726 effect on IL-6 production was mediated through concomitant reduction of NO synthesis, MPA action was mainly independent of the interference with NO generation. Finally, both agents inhibited IFN-gamma/LPS-triggered IL-6 production in mouse primary fibroblasts, but not in mouse peritoneal macrophages, indicating cell-specificity of this novel anti-inflammatory action of A77 1726 and MPA.",
publisher = "Elsevier",
journal = "Cytokine",
title = "Immunosuppressants leflunomide and mycophenolic acid inhibit fibroblast IL-6 production by distinct mechanisms",
number = "4",
volume = "19",
doi = "10.1006/cyto.2002.0885",
pages = "181-186"
}

Miljković, Đ., Samardzić, T., Drakulić, D., Stošić-Grujičić, S.,& Trajković, V.. (2002). Immunosuppressants leflunomide and mycophenolic acid inhibit fibroblast IL-6 production by distinct mechanisms. in Cytokine
Elsevier., 19(4), 181-186.
https://doi.org/10.1006/cyto.2002.0885

Miljković Đ, Samardzić T, Drakulić D, Stošić-Grujičić S, Trajković V. Immunosuppressants leflunomide and mycophenolic acid inhibit fibroblast IL-6 production by distinct mechanisms. in Cytokine. 2002;19(4):181-186.
doi:10.1006/cyto.2002.0885 .

Miljković, Đorđe, Samardzić, Tatjana, Drakulić, Danijela, Stošić-Grujičić, Stanislava, Trajković, Vladimir, "Immunosuppressants leflunomide and mycophenolic acid inhibit fibroblast IL-6 production by distinct mechanisms" in Cytokine, 19, no. 4 (2002):181-186,
https://doi.org/10.1006/cyto.2002.0885 . .

TY  - JOUR
AU  - Trajković, Vladimir
AU  - Stošić-Grujičić, Stanislava
AU  - Samardzić, Tatjana
AU  - Marković, Miloš
AU  - Miljković, Đorđe
AU  - Ramić, Zorica
AU  - Mostarica Stojković, Marija
PY  - 2001
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5997
AB  - The effect of interleukin-17 (IL-17) on production of nitric oxide (NO) in rodent astrocytes was investigated. While IL-17 by itself did not induce NO production, it caused a dose-dependent enhancement of IFN-gamma-triggered NO synthesis in both mouse and rat primary astrocytes. In contrast, IL-17 was unable to stimulate NO synthesis in either murine or rat macrophages. IFN-gamma-triggered expression of mRNA for iNOS, but not for its transcription factor interferon regulatory factor-1 (IRF-1), was markedly elevated in IL-17-treated astrocytes. The induction of iNOS mRNA by IL-17 in IFN-gamma-pretreated astrocytes was abolished by antagonists of nuclear factor-kappaB (NF-kappaB) activation--a proteasome inhibitor MG132 and an antioxidant agent PDTC, as well as with specific p38 MAP kinase inhibitor SB203580. While IL-17 stimulated both IL-1beta and IL-6 production in astrocytes, only IL-1 was partly responsible for IL-17-induced NO release. Finally, IL-17 synergized with exogenous IL-1beta and TNF-alpha for astrocyte NO production. Having in mind a well-known neurotoxic action of NO, these results suggest a possible role for IL-17 in the inflammatory diseases of the CNS.
PB  - Amsterdam: Elsevier
T2  - Journal of Neuroimmunology
T1  - Interleukin-17 stimulates inducible nitric oxide synthase activation in rodent astrocytes
IS  - 2
VL  - 119
DO  - 10.1016/s0165-5728(01)00391-5
SP  - 183
EP  - 191
ER  - 

@article{
author = "Trajković, Vladimir and Stošić-Grujičić, Stanislava and Samardzić, Tatjana and Marković, Miloš and Miljković, Đorđe and Ramić, Zorica and Mostarica Stojković, Marija",
year = "2001",
abstract = "The effect of interleukin-17 (IL-17) on production of nitric oxide (NO) in rodent astrocytes was investigated. While IL-17 by itself did not induce NO production, it caused a dose-dependent enhancement of IFN-gamma-triggered NO synthesis in both mouse and rat primary astrocytes. In contrast, IL-17 was unable to stimulate NO synthesis in either murine or rat macrophages. IFN-gamma-triggered expression of mRNA for iNOS, but not for its transcription factor interferon regulatory factor-1 (IRF-1), was markedly elevated in IL-17-treated astrocytes. The induction of iNOS mRNA by IL-17 in IFN-gamma-pretreated astrocytes was abolished by antagonists of nuclear factor-kappaB (NF-kappaB) activation--a proteasome inhibitor MG132 and an antioxidant agent PDTC, as well as with specific p38 MAP kinase inhibitor SB203580. While IL-17 stimulated both IL-1beta and IL-6 production in astrocytes, only IL-1 was partly responsible for IL-17-induced NO release. Finally, IL-17 synergized with exogenous IL-1beta and TNF-alpha for astrocyte NO production. Having in mind a well-known neurotoxic action of NO, these results suggest a possible role for IL-17 in the inflammatory diseases of the CNS.",
publisher = "Amsterdam: Elsevier",
journal = "Journal of Neuroimmunology",
title = "Interleukin-17 stimulates inducible nitric oxide synthase activation in rodent astrocytes",
number = "2",
volume = "119",
doi = "10.1016/s0165-5728(01)00391-5",
pages = "183-191"
}

Trajković, V., Stošić-Grujičić, S., Samardzić, T., Marković, M., Miljković, Đ., Ramić, Z.,& Mostarica Stojković, M.. (2001). Interleukin-17 stimulates inducible nitric oxide synthase activation in rodent astrocytes. in Journal of Neuroimmunology
Amsterdam: Elsevier., 119(2), 183-191.
https://doi.org/10.1016/s0165-5728(01)00391-5

Trajković V, Stošić-Grujičić S, Samardzić T, Marković M, Miljković Đ, Ramić Z, Mostarica Stojković M. Interleukin-17 stimulates inducible nitric oxide synthase activation in rodent astrocytes. in Journal of Neuroimmunology. 2001;119(2):183-191.
doi:10.1016/s0165-5728(01)00391-5 .

Trajković, Vladimir, Stošić-Grujičić, Stanislava, Samardzić, Tatjana, Marković, Miloš, Miljković, Đorđe, Ramić, Zorica, Mostarica Stojković, Marija, "Interleukin-17 stimulates inducible nitric oxide synthase activation in rodent astrocytes" in Journal of Neuroimmunology, 119, no. 2 (2001):183-191,
https://doi.org/10.1016/s0165-5728(01)00391-5 . .

TY  - JOUR
AU  - Trajković, Vladimir
AU  - Marković, Miloš
AU  - Samardzić, Tatjana
AU  - Miljković, Đorđe
AU  - Popadić, Dušan
AU  - Mostarica Stojković, Marija
PY  - 2001
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5996
AB  - Because the neurotoxic effects of the antifungal drug amphotericin B
(AMB) closely resemble those ascribed to the highly reactive gaseous free radical nitric
oxide (NO), we investigated the effect of AMB on NO production in rodent astrocytes.
AMB caused a dose-dependent increase of NO generation in interferon-g (IFN-g)-stimulated rat and mouse astrocytes, as well as in IFN-g 1 tumor necrosis factor-a (TNFa)-activated rat astrocytoma cell line C6. Treatment of rat astrocytes with AMB markedly potentiated IFN-g-triggered expression of mRNA for iNOS, but not for its
transcription factor IRF-1. The activation of transcription factor NF-kB was apparently
required for AMB-induced iNOS mRNA expression, as the latter was abolished by
NF-kB inhibitors: pyrrolidine dithiocarbamate and MG132. AMB-mediated enhancement of astrocyte NO production was partly dependent on endogenous IL-1, as shown by
partial inhibition of AMB effect with IL-1 receptor antagonist. IFN-g 1 AMB treatment
led to reduction of astrocyte mitochondrial respiration (measured by MTT assay) that
has been completely reverted by selective iNOS inhibitor aminoguanidine. AMB toxicity
toward IFN-g-stimulated astrocytes was dependent on both AMB and NO action, since
AMB and NO-releasing substance SNP synergized in inducing astrocyte mitochondrial
dysfunction. These results suggest that the enhancement of cytokine-induced iNOS
activation in astrocytes and the subsequent release of high amounts of NO might be at
least partly responsible for AMB neurotoxicity.
PB  - Hoboken: Wiley
T2  - Glia
T1  - Amphotericin B Potentiates the Activation of Inducible Nitric Oxide Synthase and Causes Nitric OxideDependent Mitochondrial Dysfunction in Cytokine-Treated Rodent Astrocytes
IS  - 3
VL  - 35
DO  - 10.1002/glia.1083
SP  - 180
EP  - 188
ER  - 

@article{
author = "Trajković, Vladimir and Marković, Miloš and Samardzić, Tatjana and Miljković, Đorđe and Popadić, Dušan and Mostarica Stojković, Marija",
year = "2001",
abstract = "Because the neurotoxic effects of the antifungal drug amphotericin B
(AMB) closely resemble those ascribed to the highly reactive gaseous free radical nitric
oxide (NO), we investigated the effect of AMB on NO production in rodent astrocytes.
AMB caused a dose-dependent increase of NO generation in interferon-g (IFN-g)-stimulated rat and mouse astrocytes, as well as in IFN-g 1 tumor necrosis factor-a (TNFa)-activated rat astrocytoma cell line C6. Treatment of rat astrocytes with AMB markedly potentiated IFN-g-triggered expression of mRNA for iNOS, but not for its
transcription factor IRF-1. The activation of transcription factor NF-kB was apparently
required for AMB-induced iNOS mRNA expression, as the latter was abolished by
NF-kB inhibitors: pyrrolidine dithiocarbamate and MG132. AMB-mediated enhancement of astrocyte NO production was partly dependent on endogenous IL-1, as shown by
partial inhibition of AMB effect with IL-1 receptor antagonist. IFN-g 1 AMB treatment
led to reduction of astrocyte mitochondrial respiration (measured by MTT assay) that
has been completely reverted by selective iNOS inhibitor aminoguanidine. AMB toxicity
toward IFN-g-stimulated astrocytes was dependent on both AMB and NO action, since
AMB and NO-releasing substance SNP synergized in inducing astrocyte mitochondrial
dysfunction. These results suggest that the enhancement of cytokine-induced iNOS
activation in astrocytes and the subsequent release of high amounts of NO might be at
least partly responsible for AMB neurotoxicity.",
publisher = "Hoboken: Wiley",
journal = "Glia",
title = "Amphotericin B Potentiates the Activation of Inducible Nitric Oxide Synthase and Causes Nitric OxideDependent Mitochondrial Dysfunction in Cytokine-Treated Rodent Astrocytes",
number = "3",
volume = "35",
doi = "10.1002/glia.1083",
pages = "180-188"
}

Trajković, V., Marković, M., Samardzić, T., Miljković, Đ., Popadić, D.,& Mostarica Stojković, M.. (2001). Amphotericin B Potentiates the Activation of Inducible Nitric Oxide Synthase and Causes Nitric OxideDependent Mitochondrial Dysfunction in Cytokine-Treated Rodent Astrocytes. in Glia
Hoboken: Wiley., 35(3), 180-188.
https://doi.org/10.1002/glia.1083

Trajković V, Marković M, Samardzić T, Miljković Đ, Popadić D, Mostarica Stojković M. Amphotericin B Potentiates the Activation of Inducible Nitric Oxide Synthase and Causes Nitric OxideDependent Mitochondrial Dysfunction in Cytokine-Treated Rodent Astrocytes. in Glia. 2001;35(3):180-188.
doi:10.1002/glia.1083 .

Trajković, Vladimir, Marković, Miloš, Samardzić, Tatjana, Miljković, Đorđe, Popadić, Dušan, Mostarica Stojković, Marija, "Amphotericin B Potentiates the Activation of Inducible Nitric Oxide Synthase and Causes Nitric OxideDependent Mitochondrial Dysfunction in Cytokine-Treated Rodent Astrocytes" in Glia, 35, no. 3 (2001):180-188,
https://doi.org/10.1002/glia.1083 . .

TY  - JOUR
AU  - Miljković, Đorđe
AU  - Samardžić, Tatjana
AU  - Mostarica Stojković, Marija
AU  - Stošić-Grujičić, Stanislava
AU  - Popadić, Dušan
AU  - Trajković, Vladimir
PY  - 2001
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5994
AB  - Highly reactive gaseous free radical nitric oxide (NO), generated by astrocytes and infiltrating macrophages is implicated in
inflammatory destruction of brain tissue, including that occurring in multiple sclerosis. Therefore, the influence of immunosuppressive
drug leflunomide on inducible nitric oxide synthase (iNOS)-dependent NO production in rat astrocytes and macrophages was investigated.
Under the same cultivating conditions, leflunomide’s active metabolite A77 1726 caused a dose-dependent decrease of NO production in
IFN-g1LPS-stimulated primary astrocytes, but not in macrophages. While A77 1726 did not alter iNOS enzymatic activity, it markedly
suppressed IFN-g1LPS-triggered expression of iNOS mRNA in astrocytes. In the presence of transcription inhibitor actinomycin D, A77
1726 failed to inhibit astrocyte NO production, suggesting transcriptional regulation of iNOS by leflunomide. This assumption was further
supported by the ability of A77 1726 to inhibit IFN-g1LPS-induced expression of mRNA for an important iNOS transcription factor
IRF-1. PD98059, a specific inhibitor of mitogen-activated protein kinase kinase (MAPKK/MEK), but not genistein, an unselective
protein tyrosine kinase inhibitor, completely mimicked cell type-specific inhibition of NO synthesis by A77 1726. Therefore, previously
described inhibition of MEK/MAP pathway by leflunomide could present a possible mechanism for A77 1726-mediated suppression of
iNOS activation in astrocytes. Accordingly to results obtained with primary astrocytes, both A77 1726 and PD98059 significantly reduced
IFN-g1LPS-induced NO synthesis in the cultures of rat astrocytoma cell line C6. The ability to suppress iNOS induction in astrocytes
supports potential use of leflunomide in the treatment of multiple sclerosis and other NO-dependent inflammatory brain disorders.
PB  - Elsevier Science B.V.
T2  - Brain Research
T1  - Leflunomide inhibits activation of inducible nitric oxide synthase in rat astrocytes
IS  - 1-2
VL  - 889
DO  - 10.1016/s0006-8993(00)03181-4
SP  - 331
EP  - 338
ER  - 

@article{
author = "Miljković, Đorđe and Samardžić, Tatjana and Mostarica Stojković, Marija and Stošić-Grujičić, Stanislava and Popadić, Dušan and Trajković, Vladimir",
year = "2001",
abstract = "Highly reactive gaseous free radical nitric oxide (NO), generated by astrocytes and infiltrating macrophages is implicated in
inflammatory destruction of brain tissue, including that occurring in multiple sclerosis. Therefore, the influence of immunosuppressive
drug leflunomide on inducible nitric oxide synthase (iNOS)-dependent NO production in rat astrocytes and macrophages was investigated.
Under the same cultivating conditions, leflunomide’s active metabolite A77 1726 caused a dose-dependent decrease of NO production in
IFN-g1LPS-stimulated primary astrocytes, but not in macrophages. While A77 1726 did not alter iNOS enzymatic activity, it markedly
suppressed IFN-g1LPS-triggered expression of iNOS mRNA in astrocytes. In the presence of transcription inhibitor actinomycin D, A77
1726 failed to inhibit astrocyte NO production, suggesting transcriptional regulation of iNOS by leflunomide. This assumption was further
supported by the ability of A77 1726 to inhibit IFN-g1LPS-induced expression of mRNA for an important iNOS transcription factor
IRF-1. PD98059, a specific inhibitor of mitogen-activated protein kinase kinase (MAPKK/MEK), but not genistein, an unselective
protein tyrosine kinase inhibitor, completely mimicked cell type-specific inhibition of NO synthesis by A77 1726. Therefore, previously
described inhibition of MEK/MAP pathway by leflunomide could present a possible mechanism for A77 1726-mediated suppression of
iNOS activation in astrocytes. Accordingly to results obtained with primary astrocytes, both A77 1726 and PD98059 significantly reduced
IFN-g1LPS-induced NO synthesis in the cultures of rat astrocytoma cell line C6. The ability to suppress iNOS induction in astrocytes
supports potential use of leflunomide in the treatment of multiple sclerosis and other NO-dependent inflammatory brain disorders.",
publisher = "Elsevier Science B.V.",
journal = "Brain Research",
title = "Leflunomide inhibits activation of inducible nitric oxide synthase in rat astrocytes",
number = "1-2",
volume = "889",
doi = "10.1016/s0006-8993(00)03181-4",
pages = "331-338"
}

Miljković, Đ., Samardžić, T., Mostarica Stojković, M., Stošić-Grujičić, S., Popadić, D.,& Trajković, V.. (2001). Leflunomide inhibits activation of inducible nitric oxide synthase in rat astrocytes. in Brain Research
Elsevier Science B.V.., 889(1-2), 331-338.
https://doi.org/10.1016/s0006-8993(00)03181-4

Miljković Đ, Samardžić T, Mostarica Stojković M, Stošić-Grujičić S, Popadić D, Trajković V. Leflunomide inhibits activation of inducible nitric oxide synthase in rat astrocytes. in Brain Research. 2001;889(1-2):331-338.
doi:10.1016/s0006-8993(00)03181-4 .

Miljković, Đorđe, Samardžić, Tatjana, Mostarica Stojković, Marija, Stošić-Grujičić, Stanislava, Popadić, Dušan, Trajković, Vladimir, "Leflunomide inhibits activation of inducible nitric oxide synthase in rat astrocytes" in Brain Research, 889, no. 1-2 (2001):331-338,
https://doi.org/10.1016/s0006-8993(00)03181-4 . .