Role of PKC isoforms in the FcγR‐mediated inhibition of LPS‐stimulated IL‐12 secretion by macrophages

Ligation of Fc receptors for immuno- globulin G (FcRs) inhibits lipopolysaccharide (LPS)-stimulated secretion of interleukin (IL)-12 by macrophages. FcR activation of protein kinase C (PKC) contributes to several functions of this receptor including phagocytosis, activation of the reduced nicotinamide adenine dinucleotide phos- phate oxidase, and secretion of certain cytokines. Therefore, we tested the hypothesis that PKC me- diates the FcR inhibition of IL-12 secretion by macrophages. In murine macrophages, FcR liga- tion augmented LPS-stimulated activation of PKC- and PKC- but reduced IL-12p40 secre- tion. Similarly, activation of PKC with phorbol 12-myristate 13-acetate (PMA) depressed LPS- stimulated IL-12p40 secretion, and depletion of PKC augmented LPS-stimulated IL-12p40 secre- tion. Antisense down-regulation of PKC- in- creased LPS-stimulated IL-12p40 secretion and fully prevented the effects of FcR ligation or PMA on IL-12p40 secretion. In contrast, down-regula- tion of PKC- blocked LPS-stimulated secretion of IL-12p40. Down-regulation of PKC- had no ef- fect on LPS-stimulated IL-12p40 secretion. The results suggest a negative role for PKC- and a positive role for PKC- in the regulation of LPS- stimulated IL-12p40 secretion. J. Leukoc. Biol. 79: 000-000; 2006.