Journal
JOURNAL OF NEUROCHEMISTRY
Volume 83, Issue 5, Pages 1120-1128Publisher
BLACKWELL PUBLISHING LTD
DOI: 10.1046/j.1471-4159.2002.01226.x
Keywords
astrocytes; human; interferons; nitric oxide; signal transducer and activator of transcription; tumor necrosis factor-alpha
Categories
Funding
- NIAID NIH HHS [AI44641] Funding Source: Medline
- NIMH NIH HHS [MH 55477] Funding Source: Medline
- NINDS NIH HHS [NS 11920] Funding Source: Medline
Ask authors/readers for more resources
Although interferon (IFN)-beta is firmly established as a therapeutic agent for multiple sclerosis, information regarding its role in astrocyte cytokine production is limited. In primary cultures of human astrocytes, we determined the effects of IFN-beta on astrocyte cytokine [tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6] and inducible nitric oxide synthase (iNOS) expression by ribonuclease protection assay and ELISA. We found that IFN-beta inhibited astrocyte cytokine/ iNOS induced by IL-1 plus IFN-gamma, but in the absence of IFN-gamma, IFN-beta enhanced IL-1-induced cytokine/iNOS expression. Electrophoretic mobility shift analysis (EMSA) demonstrated that IFN-gamma induced sustained IFN-gamma-activated sequence (GAS) binding, while IFN-beta induced transient GAS binding. When used together, IFN-beta inhibited IFN-gamma-induced GAS binding activity. Nuclear factor-kappa B (NF-kappaB) activation was not altered by either IFNs, whereas IFN stimulated response element (ISRE) was only activated by IFN-beta and not IFN-gamma. These results suggest that IFN-beta can both mimic and antagonize the effect of IFN-gamma by modulating induction of nuclear GAS binding activity. Our results demonstrating differential regulation of astrocyte cytokine/iNOS induction by IFN-beta are novel and have implications for inflammatory diseases of the human CNS.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available