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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2006-1-6
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pubmed:abstractText |
Interleukin (IL)-13 is a major inducer of fibrosis in many chronic infectious and autoimmune diseases. In studies of the mechanisms underlying such induction, we found that IL-13 induces transforming growth factor (TGF)-beta(1) in macrophages through a two-stage process involving, first, the induction of a receptor formerly considered to function only as a decoy receptor, IL-13Ralpha(2). Such induction requires IL-13 (or IL-4) and tumor necrosis factor (TNF)-alpha. Second, it involves IL-13 signaling through IL-13Ralpha(2) to activate an AP-1 variant containing c-jun and Fra-2, which then activates the TGFB1 promoter. In vivo, we found that prevention of IL-13Ralpha(2) expression reduced production of TGF-beta(1) in oxazolone-induced colitis and that prevention of IL-13Ralpha(2) expression, Il13ra2 gene silencing or blockade of IL-13Ralpha(2) signaling led to marked downregulation of TGF-beta(1) production and collagen deposition in bleomycin-induced lung fibrosis. These data suggest that IL-13Ralpha(2) signaling during prolonged inflammation is an important therapeutic target for the prevention of TGF-beta(1)-mediated fibrosis.
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pubmed:commentsCorrections |
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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/Bleomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/IL13RA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Il13ra1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-13,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-13 Receptor alpha1...,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Oxazolone,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-13,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/TGFB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TNFR-Fc fusion protein,
http://linkedlifedata.com/resource/pubmed/chemical/Tgfb1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
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
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1078-8956
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
99-106
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:16327802-Animals,
pubmed-meshheading:16327802-Bleomycin,
pubmed-meshheading:16327802-Blotting, Western,
pubmed-meshheading:16327802-Cell Lineage,
pubmed-meshheading:16327802-Colitis,
pubmed-meshheading:16327802-Collagen,
pubmed-meshheading:16327802-Cytokines,
pubmed-meshheading:16327802-Down-Regulation,
pubmed-meshheading:16327802-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:16327802-Fibrosis,
pubmed-meshheading:16327802-Flow Cytometry,
pubmed-meshheading:16327802-Gene Silencing,
pubmed-meshheading:16327802-Genetic Vectors,
pubmed-meshheading:16327802-Humans,
pubmed-meshheading:16327802-Immunoglobulin G,
pubmed-meshheading:16327802-Inflammation,
pubmed-meshheading:16327802-Interleukin-13,
pubmed-meshheading:16327802-Interleukin-13 Receptor alpha1 Subunit,
pubmed-meshheading:16327802-Luciferases,
pubmed-meshheading:16327802-Lung,
pubmed-meshheading:16327802-Macrophages,
pubmed-meshheading:16327802-Mice,
pubmed-meshheading:16327802-Mice, Inbred C57BL,
pubmed-meshheading:16327802-Monocytes,
pubmed-meshheading:16327802-NF-kappa B,
pubmed-meshheading:16327802-Oxazolone,
pubmed-meshheading:16327802-Promoter Regions, Genetic,
pubmed-meshheading:16327802-RNA, Small Interfering,
pubmed-meshheading:16327802-Receptors, Interleukin,
pubmed-meshheading:16327802-Receptors, Interleukin-13,
pubmed-meshheading:16327802-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:16327802-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16327802-Signal Transduction,
pubmed-meshheading:16327802-Time Factors,
pubmed-meshheading:16327802-Transcription Factor AP-1,
pubmed-meshheading:16327802-Transforming Growth Factor beta,
pubmed-meshheading:16327802-Transforming Growth Factor beta1,
pubmed-meshheading:16327802-Tumor Necrosis Factor-alpha,
pubmed-meshheading:16327802-Up-Regulation
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pubmed:year |
2006
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pubmed:articleTitle |
IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis.
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pubmed:affiliation |
Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10-CRC 5W3864, 10 Center Drive, Bethesda, Maryland 20892, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Intramural
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