Role of muIP-10 in interferon-gamma induction of Ia in rat astrocytes.
Interferon-gamma, (IFNgamma) is a potent inducer of class II MHC (Ia) in rat astrocytes and microglia which are immunocompetent cells of the central nervous system (CNS). muIP-10, a member of the alpha-chemokine family, is also induced by IFNgamma in these cells. The induction of muIP-10 mRNA occurred in an immediate early manner, while Ia mRNA-induction was delayed and required new protein synthesis. We studied the possible role of muIP-10 in IFNgamma-mediated induction of Ia in astrocytes. Antibodies to muIP-10 protein significantly inhibited the expression of surface Ia molecules by astrocytes. Incubation of astrocytes with antisense-oligonucleotides against muIP-10 mRNA also reduced the number of Ia positive cells inducible by IFNgamma. Neither the number of IFNgamma-inducible class I MHC positive cells nor the number of class I molecules expressed per cell were affected by antisense-oligonucleotides against muIP-10, indicating the specificity of the oligonucleotide and the selective requirement of muIP-10 for Ia induction by IFNgamma. Transient transfection of astrocytes with plasmids expressing muIP-10 in the antisense orientation also reduced the number of Ia positive astrocytes. These studies suggest a role for muIP-10 protein as an autocrine factor that enhances the expression of IFNgamma-inducible Ia on astrocytes. This could create focal areas rich in Ia expressing cells which could more efficiently present antigens to T cells, leading to immune-mediated inflammation such as in multiple sclerosis.
Vanguri
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Department of Neurology, University of Maryland, School of Medicine, Baltimore 21201, USA.
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D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D007371:Interferon-gamma / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines; D016376:Oligonucleotides, Antisense; D007371:Interferon-gamma