ROLE OF MUIP-10 IN INTERFERON-GAMMA INDUCTION OF IA IN RAT ASTROCYTES

Interferon-gamma (IFN gamma) 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-chemokin e family, is also induced by IFN gamma in these cells. The induction o f muIP-10 mRNA occurred in an immediate early manner, while Ia mRNA-in duction was delayed and required new protein synthesis. We studied the possible role of muIP-10 in IFN gamma-mediated induction of Ia in ast rocytes. Antibodies to muIP-10 protein significantly inhibited the exp ression of surface Ia molecules by astrocytes. Incubation of astrocyte s with antisense-oligonucleotides against muIP-10 mRNA also reduced th e number of Ia positive cells inducible by IFN gamma. Neither the numb er of IFN gamma-inducible class I MHC positive cells nor the number of class I molecules expressed per cell were affected by antisense-oligo nucleotides against muIP-10, indicating the specificity of the oligonu cleotide and the selective requirement of muIP-10 for Ia induction by IFN gamma. Transient transfection of astrocytes with plasmids expressi ng 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 IFN gamma-induc ible Ia on astrocytes. This could create focal areas rich in Ia expres sing cells which could more efficiently present antigens to T cells, l eading to immune-mediated inflammation such as in multiple sclerosis. Copyright (C) 1996 Elsevier Science Ltd.