1887

Abstract

Induction of interferon-β (IFN-β) in human (BG-9), simian (CV-1) and mouse (L-929) cell lines by Sendai virus and by poly(rI).poly(rC) has been studied for its possible dependence on protein kinase C (PKC) through the use of pharmacological inhibitors (K252a and H-7) of PKC. Exposure of BG-9, CV-1 or L-929 cells to K252a (⩾ 0.025 µ), a staurosporine derivative, 24 h before or after induction of IFN with poly(rI).poly(rC), inhibited by >95% the production of IFN-β. In contrast, virus-induced IFN production was enhanced threefold or more by K252a in BG-9 and L-929 but not in CV-1 cells. A naphthalene sulphonamide inhibitor of PKC, H-7, at ⩾5 µ, decreased poly(rI).poly(rC)-induced IFN production in BG-9 and CV-1 cells by 75 to 94%, but had no effect on IFN production in L-929 cells. Viral induction of IFN was not affected significantly by H-7 in BG-9, CV-1 and L-929 cells. In contrast to these results, the calmodulin inhibitor, trifluoperazine (5 to 15 µ) did not affect IFN-β production by poly(rI).poly(rC) but significantly enhanced IFN production by Sendai virus in both human and murine cell lines. Thus, in human and simian fibroblasts the induction of IFN-β by poly(rI).poly(rC) appears to be PKC-dependent, whereas viral induction of IFN-β is not. Results with K252a implicate PKC in non-viral induction of IFN in mouse fibroblasts, as well. Direct measurements of PKC activity in BG-9 cells exposed to several concentrations of K252a showed that the membrane PKC activity is significantly more sensitive to inhibition by K252a than is cytosolic PKC activity. In L-929 cells, K252a inhibited membrane PKC activity similarly, but was less effective as an inhibitor of cytosolic enzyme activity than in BG-9. These studies support an intregral role for PKC activity, particularly membrane-associated activity, in non-viral [poly(rI).poly(rC)] induction of IFN-β in human, simian and mouse fibroblasts.

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/content/journal/jgv/10.1099/0022-1317-71-12-2833
1990-12-01
2019-11-22
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http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-71-12-2833
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