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

被引：21

作者：

Saegusa, Kazuharu ^{[1
]}

Yotsumoto, Satoshi ^{[1
]}

Kato, Sayaka ^{[1
]}

Aramaki, Yukihiko ^{[1
]}

机构：

[1] Tokyo Univ Pharm & Life Sci, Sch Pharm, Hachioji, Tokyo 1920392, Japan

来源：

MOLECULAR IMMUNOLOGY | 2007年 / 44卷 / 06期

关键词：

CpG-ODN; PI3K; macrophages; IL-10; IL-12; p70;

D O I：

10.1016/j.molimm.2006.05.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：1323 / 1330

页数：8

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