Antiviral and antidifferentiative activities of interferon beta and gamma in relation to their induction of double-stranded RNA-dependent protein kinase activity in 3T3-L1 cells.
Mouse interferons beta (IFN-beta) and gamma (IFN-gamma) inhibit the differentiation of 3T3-L1 fibroblasts into adipocytes when added to cultures at the time of induction of differentiation. Differentiation, as measured by incorporation of radiolabeled leucine into lipids, was inhibited 50% by approximately 1-3 units/ml of either IFN-beta or IFN-gamma, with maximum inhibition of differentiation achieved with 100 units/ml of either IFN. The magnitude of antiviral activity induced by IFN-beta and IFN-gamma was similar in differentiated and undifferentiated 3T3-L1 cells, although the slopes of the dose-response curves were different; IFN-gamma induced an antiviral state with greater efficiency than IFN-beta in differentiated and undifferentiated 3T3-L1 cells. By contrast, IFN-beta induced the double-stranded RNA-dependent P1 protein kinase more efficiently than did IFN-gamma in both differentiated and undifferentiated cells. However, IFN-beta and IFN-gamma both induced greater phosphorylation of protein P1 in cell-free extracts prepared from differentiated adipocytes than in extracts from undifferentiated fibroblasts. Cultures treated with either beta or gamma IFN throughout 8 days of differentiation continued to produce double-stranded RNA-dependent protein kinase in a manner dependent on IFN dose. These results suggest that the antiviral and antidifferentiative activities of IFN-beta and IFN-gamma in 3T3-L1 cells involve different molecular mechanisms.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D007328:Insulin / Q000494:pharmacology; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D010766:Phosphorylation; D011494:Protein Kinases / Q000096:biosynthesis*; D012330:RNA, Double-Stranded / Q000378:metabolism*
D000998:Antiviral Agents; D007328:Insulin; D007370:Interferon Type I; D012330:RNA, Double-Stranded; D003907:Dexamethasone; D007371:Interferon-gamma; D011494:Protein Kinases; D015056:1-Methyl-3-isobutylxanthine