Involvement of protein kinase C in macrophage activation by poly(I.C).
The expression of cytocidal activity is initiated by the interaction of macrophages with priming [e.g., interferon (IFN)] and triggering stimuli (polyinosinic-polycytidylic acid). We have shown that the triggering step can be initiated in a Ca(2+)-dependent fashion and hypothesized that protein kinase C (PKC) may couple the Ca2+ signal to the expression of a gene product, Bf, that accompanies the expression of macrophage cytocidal activity. Exposure of IFN-primed macrophages to polyinosinic-polycytidylic acid in the presence of the PKC inhibitors H-7 or sphingosine or after downregulation of PKC with phorbol myristate acetate markedly inhibited Bf synthesis. Western blots of macrophage lysates revealed the presence of the alpha-, delta-, and zeta-isozymes of PKC, and all were found to be downregulated by phorbol myristate acetate. Inhibition of PKC also prevented the increase in IFN-beta mRNA levels and partially blocked the response to IFN-beta. These data suggest that the alpha-, delta-, and zeta-isozymes of PKC are involved in signaling leading to Bf expression and that the level of involvement is restricted to the induction and response to IFN-beta.
Lake
F R
FR
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
Dempsey
E C
EC
Spahn
J D
JD
Riches
D W
DW
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D011415:Complement Factor B / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D011070:Poly I-C / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007527:Isoenzymes; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; D016899:Interferon-beta; D007371:Interferon-gamma; D011493:Protein Kinase C; D011415:Complement Factor B; D013755:Tetradecanoylphorbol Acetate; D011070:Poly I-C