Role of muIP-10 in interferon-γ induction of Ia in rat astrocytes

Abstract

Interferon-γ (IFNγ) 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 α-chemokine family, is also induced by IFNγ 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 IFNγ-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 IFNγ. Neither the number of IFNγ-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 IFNγ. 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 IFNγ-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.