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 . .