Differing effects of IFN beta vs IFN gamma in MS - Gene expression in cultured astrocytes

Citation
J. Satoh et Y. Kuroda, Differing effects of IFN beta vs IFN gamma in MS - Gene expression in cultured astrocytes, NEUROLOGY, 57(4), 2001, pp. 681-685
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurology,"Neurosciences & Behavoir
Journal title
NEUROLOGY
ISSN journal
0028-3878 → ACNP
Volume
57
Issue
4
Year of publication
2001
Pages
681 - 685
Database
ISI
SICI code
0028-3878(20010828)57:4<681:DEOIBV>2.0.ZU;2-E
Abstract
Background: Recent clinical trials indicate that interferon-beta (IFN beta) is effective in reducing exacerbations in relapsing-remitting MS, whereas IFN-gamma provokes acute relapses. However, the molecular mechanisms underl ying the beneficial effects of IFN beta and the detrimental effects of IFN gamma in MS remain to be characterized. Previously, the authors showed that IFN beta inhibited IFN gamma -induced major histocompatibility complex (MH C) class II expression on astrocytes. Objective: To clarify the gene expres sion profile in cultured fetal human astrocytes after exposure to IFN beta, IFN gamma, or IFN beta plus IFN-gamma. Methods: Astrocytes were incubated for 24 hours in the culture medium with or without inclusion of 50 ng/mL re combinant human IFN beta, IFN-gamma, or both. The gene expression profile w as studied by analyzing a cDNA expression array containing clones of variou s functional classes. Results: Among 1,185 clones examined, the expression of six distinct genes was markedly induced after IFN treatment. Northern bl ot analysis verified a significant up-regulation of mRNA for interferon reg ulatory factor-7 (IRF-7) and pleiotrophin predominantly in astrocytes treat ed with IFN beta, both IRF-1 and intercellular adhesion molecule-1 mRNA mai nly in astrocytes treated with IFN gamma, and signal transducer and activat or of transcription-1 alpha and MHC class I HLA-C mRNA equally in astrocyte s exposed to either type of IFN. In contrast, the treatment of astrocytes w ith either IFN beta or IFN-gamma did not alter the levels of expression of mRNA for brain-derived neurotrophic factor, 27-kd heat shock protein, prion protein, or defender against apoptotic cell death-1. No antagonistic actio n was observed between IFN beta and IFN gamma in the pattern of gene induct ion in astrocytes. Conclusion: A preferential induction of IRF-7 in IFN bet a -treated astrocytes and a predominant expression of IRF-1 in IFN gamma -e xposed astrocytes might contribute to one of the molecular mechanisms under lying the clinically opposite effects of IFN beta and IFN gamma in MS.