cAMP elevators inhibit LPS-induced IL-12 p40 expression by interfering with phosphorylation of p38 MAPK in Murine Peritoneal Macrophages

被引：48

作者：

Feng, WG ^{[1
]}

Wang, YB ^{[1
]}

Zhang, JS ^{[1
]}

Wang, XY ^{[1
]}

Li, CL ^{[1
]}

Chang, ZL ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Lab Immune Signaling Transduct, Shanghai 200031, Peoples R China

来源：

CELL RESEARCH | 2002年 / 12卷 / 5-6期

关键词：

IL-12; cAMP; LPS; NF-kappa B; p38; MAPK;

D O I：

10.1038/sj.cr.7290135

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

cAMP mediated signaling may play a suppressive role in immune response. We previously found that the cAMP-elevators (CTx and 8-Br-cAMP) inhibited IL-12, IL-1a, IL-6 gene expression, but increased the transcriptional levels of IL-10 and IL-1Ra, in LPS-treated murine peritoneal macrophages. The present study examined a possible molecular mechanism involved in cAMP elevators-induced inhibition of IL-12 p40 expression in response to LPS. Our data demonstrated that cAMP elevators downregulated IL-12 p40 mRNA expression and IL-12 p70 production in murine peritoneal macrophages. Subsequent studies revealed that cAMP-elevators blocked phosphorylation of p38 MAPK, but did not affect the activity of NF-kappaB binding to IL-12 promoter (-136/-112). This is the first report that cAMP elevators inhibit LPS-induced IL-12 production by a mechanism that is associated, at least in part, with p38-dependent inhibition by cAMP signaling pathways.

引用

页码：331 / 337

页数：7

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