Interferon-gamma protects astrocytes from apoptosis and increases the formation of p21ras-GTP complex through ras oncogene family overexpression

Interferon-gamma (IFN-gamma) is a cytokine involved in the immunological ac tivation of astrocytes. Treatment of mouse astrocytes in vitro with differe nt doses of IFN-gamma induced changes in the basal expression of the primar y response genes ras studied (H-, K-, and N-ras). H-ras is heavily transcri bed in normal astrocytes, as well as in mouse brain, but its expression inc reases with IFN-gamma treatment. K and N-ras were poorly expressed by glial cells, although they also demonstrated a dose-dependent increase in expres sion after IFN-gamma treatment, with an optimal dose of 100 U/ml. As demons trated by confocal immunocytochemistry and flow cytometry, the common prote in product of the ras family, p21ras, was present in untreated cell cytopla sms and increases 169.7% in treated astrocytes. IFN-gamma treatment protect s astrocytic cells from apoptosis resulting from FCS deprivation, heat-shoc k, or staurosporine treatment, as well as increases p21 binding of GTP. The specificity of IFN-gamma induction was demonstrated when antibodies agains t this cytokine completely suppressed the overinduction of ras mRNAs and, i n perfect correlation, the biological effects reported above. We propose th at those effects are mediated through ras oncogene family everexpression. ( C) 2001 Wiley-Liss. Inc.