EFFECT OF PROTEIN-KINASE-C INHIBITORS ON INTERFERON-BETA PRODUCTION BY VIRAL AND NONVIRAL INDUCERS
Thacore, HR; Lin, HY; Davis, PJ; Schoenl, M
HERO ID
1493115
Reference Type
Journal Article
Year
1990
Language
English
PMID
| HERO ID | 1493115 |
|---|---|
| In Press | No |
| Year | 1990 |
| Title | EFFECT OF PROTEIN-KINASE-C INHIBITORS ON INTERFERON-BETA PRODUCTION BY VIRAL AND NONVIRAL INDUCERS |
| Authors | Thacore, HR; Lin, HY; Davis, PJ; Schoenl, M |
| Journal | Journal of General Virology |
| Volume | 71 |
| Issue | 12 |
| Page Numbers | 2833-2839 |
| Abstract | Induction of interferon-beta (IFN-beta) 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 (greater-than- or-equal-to 0.025 mu-M), a staurosporine derivative, 24 h before of after induction of IFN with poly(rI).poly(rC), inhibited by > 95% the production of IFN-beta. In contrast, virus-induced IFN production was enhanced threefold of more by K252a in BG-9 and L-929 but not in CV-1 cells. A naphthalene sulphonamide inhibitor of PKC, H-7, at greater-than-or-equal-to 5 mu-M, 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 mu-M) did not affect IFN-beta 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-beta by poly(rI).poly(rC) appears to be PKC-dependent, whereas viral induction of IFN-beta 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 inhibitory of cytosolic enzyme activity than in BG-9. These studies support an integral role for PKC activity, particularly membrane-associated activity, in non-viral [poly(rI).poly(rC)] induction of IFN-beta in human, simian and mouse fibroblasts. |
| Doi | 10.1099/0022-1317-71-12-2833 |
| Pmid | 2177082 |
| Wosid | WOS:A1990EP00900008 |
| Url | <Go to ISI>://WOS:A1990EP00900008 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:A1990EP00900008 |
| Is Public | Yes |
| Language Text | English |