Phosphatidylinositol 3-kinase-mediated regulation of IL-10 and IL-12 production in macrophages stimulated with CpG oligodeoxynucleotide.
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.
Saegusa
Kazuharu
K
School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Yotsumoto
Satoshi
S
Kato
Sayaka
S
Aramaki
Yukihiko
Y
D000818:Animals; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology*; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*
D009838:Oligodeoxyribonucleotides; D016753:Interleukin-10; D018664:Interleukin-12; D019869:Phosphatidylinositol 3-Kinases