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- Title
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
- Authors
Kim, Eun-Ye; Kim, Byung-Chul
- Abstract
Abstract: Smad6, one of the inhibitory Smads, plays an important role in transforming growth factor-beta1 (TGF-β1)-mediated negative regulation of pro-inflammatory signaling. In this study, we found that bacterial endotoxin lipopolysaccharide (LPS) inhibits TGF-β1-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-β1-induced Smad6 expression and its anti-inflammatory capacity. Collectively, our findings show how LPS pro-inflammatory signal antagonizes the anti-inflammatory activity of TGF-β1.
- Subjects
ENDOTOXINS; TRANSFORMING growth factors-beta; GENE expression; PHOSPHORYLATION; INTERLEUKIN-1; MITOGEN-activated protein kinases
- Publication
FEBS Letters, 2011, Vol 585, Issue 5, p779
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2011.01.044