Regulation of LPS‐stimulated IL‐10 secretion by PKC in macrophages.

Abstract

IL-10 is a potent anti-inflammatory cytokine produced by a variety of leukocytes including macrophages. It is important to understand the regulation of IL-10 because of its ability to influence the immune response and suppress inflammation. Macrophages stimulated with LPS secrete small amounts of IL-10. However, when combined with FcγR ligation LPS induces the production of large amounts of IL-10 by macrophages. The signaling pathways responsible for LPS-stimulated IL-10 and the positive effect of the FcγR on LPS-stimulated IL-10 production are not well characterized. PKC is activated by LPS and that activation is altered by FcγR ligation in macrophages. This study evaluated the role of PKC in LPS-stimulated IL-10 secretion and the effect of FcγR ligation on LPS-stimulated IL-10 secretion by mouse peritoneal macrophages. Inhibition of PKC with Gö6976 or Rottlerin decreased LPS-stimulated IL-10 secretion and rescued the effects of FcγR ligation. However, depletion of PKC-α and PKC-ε isoforms with antisense DNA oligonucleotides augmented LPS-stimulated IL-10 secretion. Depletion of PKC-δ with antisense had no effect on LPS-stimulated IL-10 secretion and did not alter the influence of FcγR ligation on LPS-stimulated IL-10 secretion. Thus PKC-δ appears to have no role in the regulation of LPS-stimulated IL-10 secretion by mouse macrophages where as PKC-α and -ε may have a negative influence on LPS-stimulated IL-10 secretion. This study was supported by the American Heart Association Grant 50893T.