Premium
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
Author(s) -
Kim Eun-Ye,
Kim Byung-Chul
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.01.044
Subject(s) - phosphorylation , transforming growth factor , lipopolysaccharide , microbiology and biotechnology , tlr4 , signal transduction , linker , psychological repression , chemistry , biology , gene , gene expression , immunology , biochemistry , computer science , operating system
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.