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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-5-28
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1460-2377
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
753-62
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Suppressor of cytokine signaling-1 ameliorates dextran sulfate sodium-induced colitis in mice.
pubmed:affiliation
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
pubmed:publicationType
Journal Article