Suppressor of cytokine signaling-1 ameliorates dextran sulfate sodium-induced colitis in mice

Jiro Horino, Minoru Fujimoto, Fumitaka Terabe, Satoshi Serada, Tsuyoshi Takahashi, Yoshihito Soma, Kentaro Tanaka, Takatoshi Chinen, Akihiko Yoshimura, Shintaro Nomura, Ichiro Kawase, Norio Hayashi, Tadamitsu Kishimoto, Tetsuji Naka

研究成果: Article査読

67 被引用数 (Scopus)

抄録

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-γ 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-γ. 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-γ, 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-γ+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-γ 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-γ/STAT1 signaling and by subsequently regulating Treg cell development.

本文言語English
ページ(範囲)753-762
ページ数10
ジャーナルInternational immunology
20
6
DOI
出版ステータスPublished - 2008 6月
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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