| First Author | Kim EY | Year | 2011 |
| Journal | FEBS Lett | Volume | 585 |
| Issue | 5 | Pages | 779-85 |
| PubMed ID | 21295571 | Mgi Jnum | J:170351 |
| Mgi Id | MGI:4946350 | Doi | 10.1016/j.febslet.2011.01.044 |
| Citation | Kim EY, et al. (2011) 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. FEBS Lett 585(5):779-85 |
| abstractText | Smad6, one of the inhibitory Smads, plays an important role in transforming growth factor-beta1 (TGF-beta1)-mediated negative regulation of pro-inflammatory signaling. In this study, we found that bacterial endotoxin lipopolysaccharide (LPS) inhibits TGF-beta1-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-beta1-induced Smad6 expression and its anti-inflammatory capacity. Collectively, our findings show how LPS pro-inflammatory signal antagonizes the anti-inflammatory activity of TGF-beta1. |
