Effect of protein kinase C inhibitors on interferon-β production by viral and non-viral inducers

H. R. Thacore, H. Y. Lin, P. J. Davis, M. Schoenl

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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 μM), 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 μM, 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 μM) 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 integral 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.

Original languageEnglish
Pages (from-to)2833-2839
Number of pages7
JournalJournal of General Virology
Volume71
Issue number12
Publication statusPublished - 1990
Externally publishedYes

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Protein C Inhibitor
Protein Kinase Inhibitors
Protein Kinase C
Interferons
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Sendai virus
Membrane Proteins
Fibroblasts
Poly I-C
Cell Line
Trifluoperazine
Staurosporine
Interferon-beta
Sulfonamides
Enzyme Inhibitors
Calmodulin
N-(1-butyl-4-phenyl-4-piperidinoyl) tetrhahydopapaverine
staurosporine aglycone
1,2-diamino-1,2-N,N'-carbonyl-1,2-dideoxyglucose hydrate
Pharmacology

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Effect of protein kinase C inhibitors on interferon-β production by viral and non-viral inducers. / Thacore, H. R.; Lin, H. Y.; Davis, P. J.; Schoenl, M.

In: Journal of General Virology, Vol. 71, No. 12, 1990, p. 2833-2839.

Research output: Contribution to journalArticle

Thacore, H. R. ; Lin, H. Y. ; Davis, P. J. ; Schoenl, M. / Effect of protein kinase C inhibitors on interferon-β production by viral and non-viral inducers. In: Journal of General Virology. 1990 ; Vol. 71, No. 12. pp. 2833-2839.
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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 μM), 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 μM, 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 μM) 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 integral 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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