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 activation of astrocytes. Treatment of mouse astrocytes in vitro with different doses of IFN-gamma induced changes in the basal expression of the primary response genes ras studied (H-, K-, and N-ras). H-ras is heavily transcribed in normal astrocytes, as well as in mouse brain, but its expression increases with IFN-gamma treatment. K and N-ras were poorly expressed by glial cells, although they also demonstrated a dose-dependent increase in expression after IFN-gamma treatment, with an optimal dose of 100 U/ml. As demonstrated by confocal immunocytochemistry and flow cytometry, the common protein product of the ras family, p21ras, was present in untreated cell cytoplasms and increases 169.7% in treated astrocytes. IFN-gamma treatment protects astrocytic cells from apoptosis resulting from FCS deprivation, heat-shock, or staurosporine treatment, as well as increases p21 binding of GTP. The specificity of IFN-gamma induction was demonstrated when antibodies against this cytokine completely suppressed the overinduction of ras mRNAs and, in perfect correlation, the biological effects reported above. We propose that those effects are mediated through ras oncogene family everexpression.
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Department of NeuroImmunology, Instituto Cajal, C.S.I.C., Dr. Arce Avenue 37, 28002 Madrid, Spain. nazario@cajal.csic.es
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism*; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D012333:RNA, Messenger; D006153:Guanosine Diphosphate; D007371:Interferon-gamma; D006160:Guanosine Triphosphate; D016283:Proto-Oncogene Proteins p21(ras)