Lipopolysaccharide inhibits transforming growth factor-beta1-stimulated Smad6 expression by inducing phosphorylation of the linker region of Smad3 through a TLR4-IRAK1-ERK1/2 pathway
Lipopolysaccharide inhibits transforming growth factor-beta1-stimulated Smad6 expression by inducing phosphorylation of the linker region of Smad3 through a TLR4-IRAK1-ERK1/2 pathway
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DOI：
10.1016/j.febslet.2011.01.044
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发表时间：
2011-03-09
期刊：
影响因子：
3.5
通讯作者：
Kim, Byung-Chul
中科院分区：
文献类型：
--
作者：
Kim, Eun-Ye;Kim, Byung-Chul
Smad 6是抑制性Smads之一，在转化生长因子β 1（TGF-β 1）介导的促炎信号负调控中发挥重要作用。在这项研究中，我们发现细菌内毒素脂多糖（LPS）抑制TGF-β 1诱导的RAW 264.7细胞中Smad 6的表达。这种抑制伴随着Thr-179和Ser-208处Smad 3连接体磷酸化的增加，并且通过TLR 4-IRAK 1连接的信号级联依赖于ERK 1/2活性。在连接区缺少磷酸化位点的突变体Smad 3的表达显著逆转了LPS对TGF-β 1诱导的Smad 6表达及其抗炎能力的抑制作用。总的来说，我们的研究结果显示了LPS促炎信号如何拮抗TGF-β 1的抗炎活性。(C)2011年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Smad6, one of the inhibitory Smads, plays an important role in transforming growth factor-beta1 (TGF-beta 1)-mediated negative regulation of pro-inflammatory signaling. In this study, we found that bacterial endotoxin lipopolysaccharide (LPS) inhibits TGF-beta 1-induced expression of Smad6 in RAW264.7 cells. This repression was accompanied by increased Smad3 linker phosphorylation at Thr-179 and Ser-208 and was dependent on ERK1/2 activity via the TLR4-IRAK1-linked signaling cascade. The expression of a mutant Smad3, that lacks the phosphorylation sites in the linker regions, significantly reversed the inhibitory effect of LPS on TGF-beta 1-induced Smad6 expression and its anti-inflammatory capacity. Collectively, our findings show how LPS pro-inflammatory signal antagonizes the anti-inflammatory activity of TGF-beta 1. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.