Interferon-gamma induces proliferation but not apoptosis in murine astrocytes through the differential expression of the myc proto-oncogene family.
Interferon-gamma (IFN-gamma) is a cytokine mainly secreted by activated T-lymphocytes. Treatment of mouse astrocytes in vitro with IFN-gamma augmented the basal expression of the primary response proto-oncogenes c-myc and L-myc as detected by Northern blotting. Such inductions were maximal at doses of 10 U/ml and after 60 min of treatment. Astrocytes fully differentiated in vitro do not express N-myc mRNA nor are induced to express it by exposure to IFN-gamma. As demonstrated by flow cytometry, the common protein product of the myc family was present in the nucleus of the cells. The specificity of IFN-gamma induction was demonstrated when antibodies against IFN-gamma completely suppressed the overinduction of these mRNAs. No apoptotic death can be detected in astrocytes treated with IFN-gamma at doses that induce c-myc expression. Conversely, treatment with a dose of 10 U/ml induced cells proliferation in astrocytic cells as measured by (3)H-thymidine incorporation.
Department of Neuroimmunology, Instituto Cajal, CSIC, Dr. Arce Avenue 37, 28002, Madrid, Spain. nazario@cajal.csic.es
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D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D053938:DNA Fragmentation; D005786:Gene Expression Regulation / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins
D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D007371:Interferon-gamma