The priming effect of human interferon-alpha is mediated by protein kinase C.
Human embryo fibroblasts (HEF) were primed when treated with a synthetic diacylglycerol, OAG, or the phorbol esters TPA or DBP. These primed HEF produce more interferon-beta (IFN-beta) in response to poly(rI).poly(rC), or poly(rA).poly(rU), added 1 h or 18 h later. These priming agents are activators of protein kinase C (PKC). A PKC inhibitor, H-7, blocked their priming effects and also those of human IFN-alpha. Two phorbol esters, 4PDD and 4P, that did not activate PKC did not prime HEF cells. Pretreatment of HEF cells for 1 h or 18 h with TPA or DBP reduced their susceptibility to infection with vesicular stomatitis virus (VSV); this effect was blocked by treatment with H-7. In contrast, the antiviral effects of IFN-alpha were not blocked by H-7, or by previous down-regulation of PKC by prolonged treatment of HEF cells with TPA. These results show that in HEF cells treated with IFN-alpha PKC plays a role in the processes that prime for IFN production, but not in those which establish the antiviral state.
Constantinescu
S N
SN
Nicolau Institute of Virology, Bucharest, Romania.
Cernescu
C
C
Balta
F
F
Maniu
H
H
Popescu
L M
LM
D002478:Cells, Cultured; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis* / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D004075:Diglycerides; D007370:Interferon Type I; D010703:Phorbol Esters; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D011070:Poly I-C