| Autor: |
Choi KC; Department of Pathology, Inha University College of Medicine and Inha Research Institute for Medical Sciences, Inha University College of Medicine by BK-21 Project, Incheon 400-712, Republic of Korea., Lee YS, Lim S, Choi HK, Lee CH, Lee EK, Hong S, Kim IH, Kim SJ, Park SH |
| Jazyk: |
angličtina |
| Zdroj: |
Nature immunology [Nat Immunol] 2006 Oct; Vol. 7 (10), pp. 1057-65. Date of Electronic Publication: 2006 Sep 03. |
| DOI: |
10.1038/ni1383 |
| Abstrakt: |
Transforming growth factor-beta1 (TGF-beta1) is a potent cytokine with pleiotropic effects, including anti-inflammatory activity. Here we show that the signaling protein Smad6 bound to Pellino-1, an adaptor protein of mammalian interleukin 1 receptor (IL-1R)-associated kinase 1 (IRAK1), and thereby promoted TGF-beta-mediated anti-inflammatory effects. Smad6-Pellino-1 interaction abrogated signaling mediated by a complex of IRAK1, Pellino-1 and adaptor protein TRAF6 that formed after stimulation by IL-1beta treatment. Blockade of IRAK1-Pellino-1-TRAF6 signaling prevented degradation of the inhibitor IkappaBalpha and subsequent nuclear translocation of transcription factor NF-kappaB and thus expression of proinflammatory genes. 'Knockdown' of endogenous Smad6 expression by RNA interference reduced anti-inflammatory activity mediated by TGF-beta1 or the TGF-beta family member BMP-4. Thus Smad6 is a critical mediator of the TGF-beta-BMP pathway that mediates anti-inflammatory activity and negatively regulates IL-1R-Toll-like receptor signals. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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