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TRAF6 Mediates IL-1β/LPS-Induced Suppression of TGF-β Signaling through Its Interaction with the Type III TGF-β Receptor
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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299683/ https://www.ncbi.nlm.nih.gov/pubmed/22427868 http://dx.doi.org/10.1371/journal.pone.0032705 |
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author | Lim, Seunghwan Bae, Eunjin Kim, Hae-Suk Kim, Tae-Aug Byun, Kyunghee Kim, Byungchul Hong, Suntaek Im, Jong Pil Yun, Chohee Lee, Bona Lee, Bonghee Park, Seok Hee Letterio, John Kim, Seong-Jin |
author_facet | Lim, Seunghwan Bae, Eunjin Kim, Hae-Suk Kim, Tae-Aug Byun, Kyunghee Kim, Byungchul Hong, Suntaek Im, Jong Pil Yun, Chohee Lee, Bona Lee, Bonghee Park, Seok Hee Letterio, John Kim, Seong-Jin |
author_sort | Lim, Seunghwan |
collection | PubMed |
description | 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 anti-inflammatory 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-κB-independent manner. TRAF6, a key molecule in IL-1β signaling, mediates this suppressive effect through interaction with the type III TGF-β receptor (TβRIII), which is TGF-β-dependent and requires type I TGF-β receptor (TβRI) kinase activity. TβRI phosphorylates TβRIII at residue S829, which promotes the TRAF6/TβRIII interaction and consequent sequestration of TβRIII from the TβRII/TβRI complex. Our data indicate that IL-1β enhances the pro-inflammatory response by suppressing TGF-βsignaling through TRAF6-mediated sequestration of TβRIII, which may be an important contributor to the early stages of tumor progression. |
format | Online Article Text |
id | pubmed-3299683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32996832012-03-16 TRAF6 Mediates IL-1β/LPS-Induced Suppression of TGF-β Signaling through Its Interaction with the Type III TGF-β Receptor Lim, Seunghwan Bae, Eunjin Kim, Hae-Suk Kim, Tae-Aug Byun, Kyunghee Kim, Byungchul Hong, Suntaek Im, Jong Pil Yun, Chohee Lee, Bona Lee, Bonghee Park, Seok Hee Letterio, John Kim, Seong-Jin PLoS One Research Article 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 anti-inflammatory 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-κB-independent manner. TRAF6, a key molecule in IL-1β signaling, mediates this suppressive effect through interaction with the type III TGF-β receptor (TβRIII), which is TGF-β-dependent and requires type I TGF-β receptor (TβRI) kinase activity. TβRI phosphorylates TβRIII at residue S829, which promotes the TRAF6/TβRIII interaction and consequent sequestration of TβRIII from the TβRII/TβRI complex. Our data indicate that IL-1β enhances the pro-inflammatory response by suppressing TGF-βsignaling through TRAF6-mediated sequestration of TβRIII, which may be an important contributor to the early stages of tumor progression. Public Library of Science 2012-03-12 /pmc/articles/PMC3299683/ /pubmed/22427868 http://dx.doi.org/10.1371/journal.pone.0032705 Text en Lim et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lim, Seunghwan Bae, Eunjin Kim, Hae-Suk Kim, Tae-Aug Byun, Kyunghee Kim, Byungchul Hong, Suntaek Im, Jong Pil Yun, Chohee Lee, Bona Lee, Bonghee Park, Seok Hee Letterio, John Kim, Seong-Jin TRAF6 Mediates IL-1β/LPS-Induced Suppression of TGF-β Signaling through Its Interaction with the Type III TGF-β Receptor |
title | TRAF6 Mediates IL-1β/LPS-Induced Suppression of TGF-β Signaling through Its Interaction with the Type III TGF-β Receptor |
title_full | TRAF6 Mediates IL-1β/LPS-Induced Suppression of TGF-β Signaling through Its Interaction with the Type III TGF-β Receptor |
title_fullStr | TRAF6 Mediates IL-1β/LPS-Induced Suppression of TGF-β Signaling through Its Interaction with the Type III TGF-β Receptor |
title_full_unstemmed | TRAF6 Mediates IL-1β/LPS-Induced Suppression of TGF-β Signaling through Its Interaction with the Type III TGF-β Receptor |
title_short | TRAF6 Mediates IL-1β/LPS-Induced Suppression of TGF-β Signaling through Its Interaction with the Type III TGF-β Receptor |
title_sort | traf6 mediates il-1β/lps-induced suppression of tgf-β signaling through its interaction with the type iii tgf-β receptor |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299683/ https://www.ncbi.nlm.nih.gov/pubmed/22427868 http://dx.doi.org/10.1371/journal.pone.0032705 |
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