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- Title
TRAF6 Mediates IL-1β/LPS-Induced Suppression of TGF-β Signaling through Its Interaction with the Type III TGF-β Receptor.
- Authors
Seunghwan Lim; Eunjin Bae; Hae-Suk Kim; Tae-Aug Kim; Kyunghee Byun; Byungchul Kim; Suntaek Hong; Jong Pil Im; Chohee Yun; Bona Lee; Bonghee Lee; Seok Hee Park; John Letterio; Seong-Jin Kim
- Abstract
Transforming growth factor-β1 (TGF-β1) is an important anti-inflammatory cytokine that modulates and resolves inflammatory responses. Recent studies have demonstrated that inflammation enhances neoplastic risk and potentiates tumor progression. In the evolution of cancer, pro-inflammatory cytokines such as IL-1β must overcome the antiinflammatory effects of TGF-β to boost pro-inflammatory responses in epithelial cells. Here we show that IL-1β or Lipopolysaccharide (LPS) suppresses TGF-β-induced anti-inflammatory signaling in a NF-kB-independent manner. TRAF6, a key molecule in IL-1β signaling, mediates this suppressive effect through interaction with the type III TGF-b receptor (TβRIII), which is TGF-β-dependent and requires type I TGF-β receptor (TβRI) kinase activity. TbRI phosphorylates TbRIII at residue S829, which promotes the TRAF6/TβRIII interaction and consequent sequestration of TβRIII from the TbRII/TbRI complex. Our data indicate that IL-1b enhances the pro-inflammatory response by suppressing TGF-bsignaling through TRAF6- mediated sequestration of TβRIII, which may be an important contributor to the early stages of tumor progression.
- Subjects
TRANSFORMING growth factors; CYTOKINES; EPITHELIAL cells; LIPOPOLYSACCHARIDES; IMMUNOREGULATION; IMMUNOMODULATORS
- Publication
PLoS ONE, 2012, Vol 7, Issue 3, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0032705