Journal
FEBS LETTERS
Volume 585, Issue 5, Pages 779-785Publisher
WILEY
DOI: 10.1016/j.febslet.2011.01.044
Keywords
TGF-beta 1; Smad6; LPS; IRAK1; ERK1/2; Smad3 linker phosphorylation
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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.
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