Serum amyloid A is an endogenous ligand that differentially induces IL-12 and IL-23
Serum amyloid A is an endogenous ligand that differentially induces IL-12 and IL-23
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DOI：
10.4049/jimmunol.177.6.4072
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发表时间：
2006-09-15
影响因子：
4.4
通讯作者：
Ye, Richard D.
中科院分区：
文献类型：
--
作者：
He, Rong;Shepard, Larry W.;Ye, Richard D.
急性时相蛋白C反应蛋白和血清淀粉样蛋白A（SAA）是感染和炎症的生物标志物。然而，它们在免疫和炎症中的确切作用仍然不确定。我们在这项研究中报告了SAA在Th 1型免疫调节细胞因子IL-12和IL-23的差异诱导中的一种新特性。在外周血单核细胞和THP-1单核细胞系中，SAA诱导IL-12和IL-23共有的亚基IL-12 p40的表达。SAA刺激的IL-12 p40的表达是快速的（= 20小时）、有效的（24小时内高达3380 pg/ml/10（6）个细胞），并且对多粘菌素B处理不敏感。SAA刺激的IL-12 p40分泌需要从头蛋白质合成，并伴有转录因子NF-κ B和C/EBP的激活。IL-12 p40的表达需要p38 MAPK和PI 3 K的激活。有趣的是，SAA诱导的IL-12 p40产生伴随着IL-23 p19的持续表达，而不是IL-12 p35，导致IL-23的优先分泌，而不是IL-12。这些结果将SAA鉴定为潜在激活IL-23/IL-17通路的内源性配体，并提出了通过急性期蛋白调节炎症和免疫的新机制。
The acute-phase proteins, C-reactive protein and serum amyloid A (SAA), are biomarkers of infection and inflammation. However, their precise role in immunity and inflammation remains undefined. We report in this study a novel property of SAA in the differential induction of Th1-type immunomodulatory cytokines IL-12 and IL-23. In peripheral blood monocytes and the THP-1 monocytic cell line, SAA induces the expression of IL-12p40, a subunit shared by IL-12 and IL-23. SAA-stimulated expression of IL-12p40 was rapid (= 20 h), potent (up to 3380 pg/ml/10(6) cells in 24 h), and insensitive to polymyxin B treatment. The SAA-stimulated IL-12p40 secretion required de novo protein synthesis and was accompanied by activation of the transcription factors NF-kappa B and C/EBP. Expression of IL-12p40 required activation of the p38 MAPK and PI3K. Interestingly, the SAA-induced IL-12p40 production was accompanied by a sustained expression of IL-23p19, but not IL-12p35, resulting in preferential secretion of IL-23, but not IL-12. These results identify SAA as an endogenous ligand that potentially activates the IL-23/IL-17 pathway and present a novel mechanism for regulation of inflammation and immunity by an acute-phase protein.