ANALYSIS OF B7-1 AND B7-2 COSTIMULATORY LIGANDS IN CULTURED MOUSE MICROGLIA - UP-REGULATION BY INTERFERON-GAMMA AND LIPOPOLYSACCHARIDE AND DOWN-REGULATION BY INTERLEUKIN-10, PROSTAGLANDIN E(2) AND CYCLIC AMP-ELEVATING AGENTS

Recent evidence indicates that membrane-bound costimulatory molecules of the B7 family are important for T-cell activation and are upregulat ed in IFN gamma-stimulated human microglia and in multiple sclerosis a ctive lesions. In this study we have performed a detailed analysis of B7-1 and B7-2 expression and regulation in cultured mouse glial cells using immunocytochemical and semi-quantitative reverse transcriptase-p olymerase chain reaction techniques. In an immortalized mouse microgli al cell Line (BV-2), expression of B7-1 and B7-2 was enhanced by inter feron-gamma (IFN gamma). IFN gamma was a weak inducer of B7-2 mRNA and immunoreactivity in microglia primary cultures obtained from the neon atal mouse brain, whereas lipopolysaccharide, tumour necrosis factor-a lpha, colony-stimulating factors and interleukin-1 beta did not affect microglial B7-2 expression. Combined IFN gamma and lipopolysaccharide treatment very effectively upregulated the B7-2 gene expression and i mmunoreactivity in microglia, but not in astrocytes. In both glial cel l types, expression of B7-1 was not induced by any of the above agents . Among known microglia/macrophage deactivators, interleukin-10, prost aglandin E(2) and cAMP-elevating agents, but not transforming growth f actor-beta(1) and interleukin-4, inhibited B7-2 transcripts and immuno reactivity in IFN gamma/LPS-stimulated microglia, thus suggesting poss ible paracrine and autocrine mechanisms for regulating the expression of this important T-cell costimulatory signal in the brain.