TY  - JOUR
AU  - Miljković, Đorđe
AU  - Samardžić, Tatjana
AU  - Stojanović, Ivana D.
AU  - Mostarica Stojković, Marija
AU  - Trajković, Vladimir
PY  - 2002
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5921
AB  - Free radical nitric oxide (NO), generated by inducible nitric oxide synthase (iNOS) in astrocytes and macrophages, has been implicated in CNS inflammatory disorders such as multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Mycophenolic acid (MPA), a selective inhibitor of inosine monophosphate dehydrogenase (IMPDH), inhibited interferon-gamam (IFN-gamma)  lipopolysaccharide (LPS)-induced NO production dose-dependently in astrocytes, but not in macrophages. The effect of MPA was not mediated through interference with IMPDHdependent synthesis of iNOS cofactor BH4 and subsequent suppression of iNOS enzymatic activity, as direct BH4 precursor sepiapterin failed to block the action of the drug. However, MPA markedly inhibited IFN-gamma  LPS-triggered astrocyte expression of mRNA for iNOS and its transcription factor IRF-1, while the expression of tumor necrosis factor- (TNF-) gene was not altered. The observed MPA suppression of NO release and iNOS and IRF-1 induction in astrocytes were efficiently prevented by exogenous guanosine, indicating that the drug acted through reduction of IMPDH dependent synthesis of guanosine nucleotides. This IRF-1-dependent inhibition of iNOS activation might be partly responsible for the protective effect of MPA in EAE, prompting investigation of its potential use in multiple sclerosis
PB  - Hoboken: Wiley
T2  - Glia
T1  - Mycophenolic acid downregulates inducible nitric oxide synthase induction in astrocytes
IS  - 3
VL  - 39
DO  - 10.1002/glia.10089
SP  - 247
EP  - 255
ER  - 

@article{
author = "Miljković, Đorđe and Samardžić, Tatjana and Stojanović, Ivana D. and Mostarica Stojković, Marija and Trajković, Vladimir",
year = "2002",
abstract = "Free radical nitric oxide (NO), generated by inducible nitric oxide synthase (iNOS) in astrocytes and macrophages, has been implicated in CNS inflammatory disorders such as multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Mycophenolic acid (MPA), a selective inhibitor of inosine monophosphate dehydrogenase (IMPDH), inhibited interferon-gamam (IFN-gamma)  lipopolysaccharide (LPS)-induced NO production dose-dependently in astrocytes, but not in macrophages. The effect of MPA was not mediated through interference with IMPDHdependent synthesis of iNOS cofactor BH4 and subsequent suppression of iNOS enzymatic activity, as direct BH4 precursor sepiapterin failed to block the action of the drug. However, MPA markedly inhibited IFN-gamma  LPS-triggered astrocyte expression of mRNA for iNOS and its transcription factor IRF-1, while the expression of tumor necrosis factor- (TNF-) gene was not altered. The observed MPA suppression of NO release and iNOS and IRF-1 induction in astrocytes were efficiently prevented by exogenous guanosine, indicating that the drug acted through reduction of IMPDH dependent synthesis of guanosine nucleotides. This IRF-1-dependent inhibition of iNOS activation might be partly responsible for the protective effect of MPA in EAE, prompting investigation of its potential use in multiple sclerosis",
publisher = "Hoboken: Wiley",
journal = "Glia",
title = "Mycophenolic acid downregulates inducible nitric oxide synthase induction in astrocytes",
number = "3",
volume = "39",
doi = "10.1002/glia.10089",
pages = "247-255"
}

Miljković, Đ., Samardžić, T., Stojanović, I. D., Mostarica Stojković, M.,& Trajković, V.. (2002). Mycophenolic acid downregulates inducible nitric oxide synthase induction in astrocytes. in Glia
Hoboken: Wiley., 39(3), 247-255.
https://doi.org/10.1002/glia.10089

Miljković Đ, Samardžić T, Stojanović ID, Mostarica Stojković M, Trajković V. Mycophenolic acid downregulates inducible nitric oxide synthase induction in astrocytes. in Glia. 2002;39(3):247-255.
doi:10.1002/glia.10089 .

Miljković, Đorđe, Samardžić, Tatjana, Stojanović, Ivana D., Mostarica Stojković, Marija, Trajković, Vladimir, "Mycophenolic acid downregulates inducible nitric oxide synthase induction in astrocytes" in Glia, 39, no. 3 (2002):247-255,
https://doi.org/10.1002/glia.10089 . .

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  - Stošić-Grujičić, Stanislava
AU  - Maksimović-Ivanić, Danijela
AU  - Mostarica Stojković, Marija
AU  - Lukić, Miodrag
PY  - 2001
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3790
AB  - Xanthine derivative, pentoxifylline (PTX), has been recently shown to exert a protective effects in certain animal models of autoimmunity, including diabetes in NOD mice. In the present study, the immunomodulatory potential of PTX was investigated in autoimmune diabetes induced by multiple low doses of streptozotocin (MLD-SZ) in genetically susceptible CBA/H mice (tested with 40 mg SZ/kg b.w. for 5 days) and DA rats (tested with 20 mg/kg b.w. for 5 days). In both species, 2-3 weeks following the MLD-SZ treatment, sustained hyperglycemia developed, as an outcome of inflammatory reaction with endothelial cell activation and accumulation of mononuclear cells. Although there was no evidence of typical insulitis in early disease development (day 10), in both rats and mice, macrophages, CD4+ and CD8+ cells were present in the islets of Langerhans as diffuse mononuclear infiltrates with the expression of IFN-gamma, and inducible NO synthase (iNOS). Administration of PTX (200 mg/kg/day for 10 days) in combination with MLD-SZ reduced insulitis and the production of mediators tested, and prevented the development of hyperglycemia. These results suggest that beneficial effects of PTX involve down-regulation of local proinflammatory cytokine-mediated NO synthase pathway. They also demonstrate that in addition to ameliorating spontaneous autoimmunity in NOD mice, PTX may be effective in downregulating an inflammatory autoimmune process triggered in susceptible host by an external agents, such as streptozotocin.
PB  - Hindawi Publishing Corporation
T2  - Developmental Immunology
T1  - Pentoxifylline prevents autoimmune mediated inflammation in low dose streptozotocin induced diabetes
IS  - 3-4
VL  - 8
DO  - 10.1155/2001/37209
SP  - 213
EP  - 221
ER  - 

@article{
author = "Stošić-Grujičić, Stanislava and Maksimović-Ivanić, Danijela and Mostarica Stojković, Marija and Lukić, Miodrag",
year = "2001",
abstract = "Xanthine derivative, pentoxifylline (PTX), has been recently shown to exert a protective effects in certain animal models of autoimmunity, including diabetes in NOD mice. In the present study, the immunomodulatory potential of PTX was investigated in autoimmune diabetes induced by multiple low doses of streptozotocin (MLD-SZ) in genetically susceptible CBA/H mice (tested with 40 mg SZ/kg b.w. for 5 days) and DA rats (tested with 20 mg/kg b.w. for 5 days). In both species, 2-3 weeks following the MLD-SZ treatment, sustained hyperglycemia developed, as an outcome of inflammatory reaction with endothelial cell activation and accumulation of mononuclear cells. Although there was no evidence of typical insulitis in early disease development (day 10), in both rats and mice, macrophages, CD4+ and CD8+ cells were present in the islets of Langerhans as diffuse mononuclear infiltrates with the expression of IFN-gamma, and inducible NO synthase (iNOS). Administration of PTX (200 mg/kg/day for 10 days) in combination with MLD-SZ reduced insulitis and the production of mediators tested, and prevented the development of hyperglycemia. These results suggest that beneficial effects of PTX involve down-regulation of local proinflammatory cytokine-mediated NO synthase pathway. They also demonstrate that in addition to ameliorating spontaneous autoimmunity in NOD mice, PTX may be effective in downregulating an inflammatory autoimmune process triggered in susceptible host by an external agents, such as streptozotocin.",
publisher = "Hindawi Publishing Corporation",
journal = "Developmental Immunology",
title = "Pentoxifylline prevents autoimmune mediated inflammation in low dose streptozotocin induced diabetes",
number = "3-4",
volume = "8",
doi = "10.1155/2001/37209",
pages = "213-221"
}

Stošić-Grujičić, S., Maksimović-Ivanić, D., Mostarica Stojković, M.,& Lukić, M.. (2001). Pentoxifylline prevents autoimmune mediated inflammation in low dose streptozotocin induced diabetes. in Developmental Immunology
Hindawi Publishing Corporation., 8(3-4), 213-221.
https://doi.org/10.1155/2001/37209

Stošić-Grujičić S, Maksimović-Ivanić D, Mostarica Stojković M, Lukić M. Pentoxifylline prevents autoimmune mediated inflammation in low dose streptozotocin induced diabetes. in Developmental Immunology. 2001;8(3-4):213-221.
doi:10.1155/2001/37209 .

Stošić-Grujičić, Stanislava, Maksimović-Ivanić, Danijela, Mostarica Stojković, Marija, Lukić, Miodrag, "Pentoxifylline prevents autoimmune mediated inflammation in low dose streptozotocin induced diabetes" in Developmental Immunology, 8, no. 3-4 (2001):213-221,
https://doi.org/10.1155/2001/37209 . .