biostudies-literatureUnknown7(3)Lim STransforming growth factor-?1 (TGF-?1) 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-1? must overcome the anti-inflammatory effects of TGF-? to boost pro-inflammatory responses in epithelial cells. Here we show that IL-1? or Lipopolysaccharide (LPS) suppresses TGF-?-induced anti-inflammatory signaling in a NF-?B-independent manner. TRAF6, a key molecule in IL-1? signaling, mediates this suppressive effect through interaction with the type III TGF-? receptor (T?RIII), which is TGF-?-dependent and requires type I TGF-? receptor (T?RI) kinase activity. T?RI phosphorylates T?RIII at residue S829, which promotes the TRAF6/T?RIII interaction and consequent sequestration of T?RIII from the T?RII/T?RI complex. Our data indicate that IL-1? enhances the pro-inflammatory response by suppressing TGF-? signaling through TRAF6-mediated sequestration of T?RIII, which may be an important contributor to the early stages of tumor progression.PloS onee32705https://www.ebi.ac.uk/biostudies/studies/S-EPMC3299683biostudies-literatureTRAF6 mediates IL-1?/LPS-induced suppression of TGF-? signaling through its interaction with the type III TGF-? receptor.PMC3299683Lim SKim BBae EByun KKim HSYun CKim TALetterio JLee BIm JPPark SHKim SJHong SfalseTRAF6 mediates IL-1?/LPS-induced suppression of TGF-? signaling through its interaction with the type III TGF-? receptor.Transforming growth factor-?1 (TGF-?1) 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-1? must overcome the anti-inflammatory effects of TGF-? to boost pro-inflammatory responses in epithelial cells. Here we show that IL-1? or Lipopolysaccharide (LPS) suppresses TGF-?-induced anti-inflammatory signaling in a NF-?B-independent manner. TRAF6, a key molecule in IL-1? signaling, mediates this suppressive effect through interaction with the type III TGF-? receptor (T?RIII), which is TGF-?-dependent and requires type I TGF-? receptor (T?RI) kinase activity. T?RI phosphorylates T?RIII at residue S829, which promotes the TRAF6/T?RIII interaction and consequent sequestration of T?RIII from the T?RII/T?RI complex. Our data indicate that IL-1? enhances the pro-inflammatory response by suppressing TGF-? signaling through TRAF6-mediated sequestration of T?RIII, which may be an important contributor to the early stages of tumor progression.2012-01-01T00:00:00Z20122021-03-06T08:47:52Z2019-03-26T23:12:47ZS-EPMC32996832242786810.1371/journal.pone.0032705