Source:http://linkedlifedata.com/resource/pubmed/id/18381351
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2008-5-28
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pubmed:abstractText |
Inflammatory bowel disease (IBD) is a chronic disorder of the gastrointestinal tract. Although the etiology and pathogenesis of IBD remain unknown, pro-inflammatory cytokines including IFN-gamma play an important role in the development of IBD. Suppressor of cytokine signaling-1 (SOCS-1) is a crucial inhibitor of cytokine signaling, particularly of IFN-gamma. In this study, we investigated the role of SOCS-1 in the development of murine dextran sulfate sodium (DSS)-induced colitis, a model of colitis resembling human IBD. SOCS-1 heterozygous (SOCS-1(+/-)) and wild-type (WT) mice were given 3% DSS dissolved in drinking water for 5 days. Activation and expression of signal transducers and activators of transcription (STAT) in colonic tissues were assessed by western blot analysis. The expression of CD4, IFN-gamma, IL-4, IL-17 and Forkhead box P3 (Foxp3) in colonic lamina propria lymphocytes was analyzed by flow cytometry and cytokine concentrations in serum were measured. DSS-treated SOCS-1(+/-) mice developed more severe colitis than DSS-treated WT mice. Enhanced activation of STAT1, a higher ratio of CD4(+)IFN-gamma(+) T cells and a lower frequency of Foxp3(+) regulatory T (Treg) cells, were observed in the colon of DSS-treated SOCS-1(+/-) mice compared with DSS-treated WT mice. DSS-treated SOCS-1(+/-) mice showed higher levels of IFN-gamma in sera than did DSS-treated WT mice. Furthermore, T cell-specific SOCS-1-conditional knockout mice developed more severe colitis than control mice after DSS administration. Our findings suggest that SOCS-1, particularly in T cells, prevents the development of DSS-induced colitis in mice by inhibiting IFN-gamma/STAT1 signaling and by subsequently regulating Treg cell development.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Dextran Sulfate,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Foxp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Socs1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Stat1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling...
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1460-2377
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pubmed:author |
pubmed-author:ChinenTakatoshiT,
pubmed-author:FujimotoMinoruM,
pubmed-author:HayashiNorioN,
pubmed-author:HorinoJiroJ,
pubmed-author:KawaseIchiroI,
pubmed-author:KishimotoTadamitsuT,
pubmed-author:NakaTetsujiT,
pubmed-author:NomuraShintaroS,
pubmed-author:SeradaSatoshiS,
pubmed-author:SomaYoshihitoY,
pubmed-author:TakahashiTsuyoshiT,
pubmed-author:TanakaKentaroK,
pubmed-author:TerabeFumitakaF,
pubmed-author:YoshimuraAkihikoA
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pubmed:issnType |
Electronic
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
753-62
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pubmed:meshHeading |
pubmed-meshheading:18381351-Animals,
pubmed-meshheading:18381351-CD4-Positive T-Lymphocytes,
pubmed-meshheading:18381351-Colitis,
pubmed-meshheading:18381351-Dextran Sulfate,
pubmed-meshheading:18381351-Disease Models, Animal,
pubmed-meshheading:18381351-Forkhead Transcription Factors,
pubmed-meshheading:18381351-Inflammatory Bowel Diseases,
pubmed-meshheading:18381351-Interferon-gamma,
pubmed-meshheading:18381351-Mice,
pubmed-meshheading:18381351-Mice, Knockout,
pubmed-meshheading:18381351-Mucous Membrane,
pubmed-meshheading:18381351-STAT1 Transcription Factor,
pubmed-meshheading:18381351-Suppressor of Cytokine Signaling Proteins,
pubmed-meshheading:18381351-T-Lymphocytes, Regulatory
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pubmed:year |
2008
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pubmed:articleTitle |
Suppressor of cytokine signaling-1 ameliorates dextran sulfate sodium-induced colitis in mice.
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pubmed:affiliation |
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
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pubmed:publicationType |
Journal Article
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