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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2005-2-14
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pubmed:abstractText |
Transforming growth factor-beta1 (TGF-beta1) is a multifunctional, potent anti-inflammatory cytokine produced by many cell types that regulates cell proliferation, apoptosis, and immune responses. Toll-like receptors (TLRs) recognize various pathogen-associated molecular patterns and are therefore a pivotal component of the innate immune system. In this study we show that TGF-beta1 blocks the NF-kappaB activation and cytokine release that is stimulated by ligands for TLRs 2, 4, and 5. We further show that TGF-beta1 can specifically interfere with TLR2, -4, or -5 ligand-induced responses involving the adaptor molecule MyD88 (myeloid differentiation factor 88) but not the TRAM/TRIF signaling pathway by decreasing MyD88 protein levels in a dose- and time-dependent manner without altering its mRNA expression. The proteasome inhibitor epoxomicin abolished the MyD88 degradation induced by TGF-beta1. Furthermore, TGF-beta1 resulted in ubiquitination of MyD88 protein, suggesting that TGF-beta1 facilitates ubiquitination and proteasomal degradation of MyD88 and thereby attenuates MyD88-dependent signaling by decreasing cellular levels of MyD88 protein. These findings importantly contribute to our understanding of molecular mechanisms mediating anti-inflammatory modulation of immune responses by TGF-beta1.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Vesicular...,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL5,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/MYD88 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myeloid Differentiation Factor 88,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/TGFB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TICAM1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TLR2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TLR4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TRAM protein, ER, mammalian,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5491-5
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15623538-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:15623538-Adaptor Proteins, Vesicular Transport,
pubmed-meshheading:15623538-Antigens, Differentiation,
pubmed-meshheading:15623538-Cell Line,
pubmed-meshheading:15623538-Chemokine CCL5,
pubmed-meshheading:15623538-Endothelial Cells,
pubmed-meshheading:15623538-Humans,
pubmed-meshheading:15623538-Interferon-gamma,
pubmed-meshheading:15623538-Ligands,
pubmed-meshheading:15623538-Lipopolysaccharides,
pubmed-meshheading:15623538-Membrane Glycoproteins,
pubmed-meshheading:15623538-Myeloid Differentiation Factor 88,
pubmed-meshheading:15623538-NF-kappa B,
pubmed-meshheading:15623538-Proteasome Endopeptidase Complex,
pubmed-meshheading:15623538-RNA, Messenger,
pubmed-meshheading:15623538-Receptors, Cell Surface,
pubmed-meshheading:15623538-Receptors, Immunologic,
pubmed-meshheading:15623538-Signal Transduction,
pubmed-meshheading:15623538-Toll-Like Receptor 2,
pubmed-meshheading:15623538-Toll-Like Receptor 4,
pubmed-meshheading:15623538-Toll-Like Receptors,
pubmed-meshheading:15623538-Transforming Growth Factor beta,
pubmed-meshheading:15623538-Transforming Growth Factor beta1,
pubmed-meshheading:15623538-Tumor Necrosis Factor-alpha,
pubmed-meshheading:15623538-Ubiquitin
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pubmed:year |
2005
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pubmed:articleTitle |
Transforming growth factor-beta differentially inhibits MyD88-dependent, but not TRAM- and TRIF-dependent, lipopolysaccharide-induced TLR4 signaling.
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pubmed:affiliation |
Department of Pediatric Infectious Diseases, Cedars-Sinai Medical Center, University of California Los Angeles, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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