TRAF6 mediates IL-1ß/LPS-induced suppression of TGF-ß signaling through its interaction with the type III TGF-ß receptor.
PLoS One
; 7(3): e32705, 2012.
Article
em En
| MEDLINE
| ID: mdl-22427868
ABSTRACT
Transforming growth factor-ß1 (TGF-ß1) 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-1ß must overcome the anti-inflammatory effects of TGF-ß to boost pro-inflammatory responses in epithelial cells. Here we show that IL-1ß or Lipopolysaccharide (LPS) suppresses TGF-ß-induced anti-inflammatory signaling in a NF-κB-independent manner. TRAF6, a key molecule in IL-1ß signaling, mediates this suppressive effect through interaction with the type III TGF-ß receptor (TßRIII), which is TGF-ß-dependent and requires type I TGF-ß receptor (TßRI) kinase activity. TßRI phosphorylates TßRIII at residue S829, which promotes the TRAF6/TßRIII interaction and consequent sequestration of TßRIII from the TßRII/TßRI complex. Our data indicate that IL-1ß enhances the pro-inflammatory response by suppressing TGF-ß signaling through TRAF6-mediated sequestration of TßRIII, which may be an important contributor to the early stages of tumor progression.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteoglicanas
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Transdução de Sinais
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Fator de Crescimento Transformador beta
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Receptores de Fatores de Crescimento Transformadores beta
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Fator 6 Associado a Receptor de TNF
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Interleucina-1beta
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Inflamação
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article