Phosphatidylinositol 3-kinase-mediated regulation of IL-10 and IL-12 production in macrophages stimulated with CpG oligodeoxynucleotide

Mol Immunol. 2007 Feb;44(6):1323-30. doi: 10.1016/j.molimm.2006.05.008. Epub 2006 Jul 5.


The aim of this study was to clarify the role of phosphatidylinositol 3-kinase (PI3K) on the production of interleukine-10 (IL-10) and IL-12 in mouse peritoneal macrophages stimulated with CpG-ODN. CpG-ODN-induced IL-10 mRNA expression and protein production decreased following the treatment of macrophages with wortmannin and LY294002, specific inhibitors for PI3K. In contrast, IL-12 p40 mRNA expression and p70 protein production increased. Neutralizing anti-IL-10 monoclonal antibody (anti-IL-10 mAb) exactly mimicked the effects of PI3K inhibitors to enhance IL-12 p70 production. The enhancement effect of PI3K inhibitors on IL-12 p70 production almost completely disappeared by the treatment with anti-IL-10 mAb. PI3K inhibitors suppressed the activation of extracellular-regulated kinase (ERK), a member of the mitogen-activated protein kinases, by CpG-ODN. A specific ERK inhibitor, U0126, as well as PI3K inhibitors, differentially regulated IL-10 and IL-12 p70 productions. These results suggest that PI3K positively and negatively regulates the production of CpG-ODN-induced IL-10 and IL-12 p70, respectively, and negatively regulates IL-12 p70 production in macrophages through ERK-mediated IL-10 induction.

MeSH terms

  • Animals
  • Cells, Cultured
  • CpG Islands / immunology*
  • Enzyme Activation / genetics
  • Enzyme Activation / immunology
  • Interleukin-10 / biosynthesis*
  • Interleukin-12 / biosynthesis*
  • Macrophages, Peritoneal / enzymology
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Oligodeoxyribonucleotides / immunology*
  • Phosphatidylinositol 3-Kinases / physiology*


  • Oligodeoxyribonucleotides
  • Interleukin-10
  • Interleukin-12
  • Phosphatidylinositol 3-Kinases