Ameliorating effect of anti-Fas ligand MAb on wasting disease in murine model of chronic colitis

N. Dan, T. Kanai, T. Totsuka, R. Iiyama, M. Yamazaki, T. Sawada, T. Miyata, H. Yagita, K. Okumura, M. Watanabe

研究成果: Article査読

12 被引用数 (Scopus)

抄録

Fas/Fas ligand (FasL) interaction has been implicated in the pathogenesis of various diseases. To clarify the involvement of Fas/FasL in the pathogenesis of intestinal inflammation, we investigated the preventive and therapeutic effects of neutralizing anti-FasL monoclonal antibody (MAb) on the development of chronic colitis induced by adaptive transfer of CD4+CD45RB high T cells to SCID mice. Administration of anti-FasL MAb from 1 day after T cell transfer (prevention study) resulted in a significant improvement of clinical manifestations such as wasting and diarrhea. However, histological examination showed that mucosal inflammation in the colon, such as infiltration of T cells and macrophages, was not improved by the anti-FasL MAb treatment. In vitro studies showed that anti-FasL MAb did not inhibit IFN-γ production by anti-CD3/CD28-stimulated lamina propria CD4 + T cells but suppressed TNF-α and IL-1β production by lamina propria mononuclear cells. Therapeutic administration of anti-FasL MAb from 3 wk after T cell transfer also improved ongoing wasting disease but not intestinal inflammation. These results suggest that the Fas/FasL interaction plays a critical role in regulating systemic wasting disease but not local intestinal inflammation.

本文言語English
ページ(範囲)G754-G760
ジャーナルAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
285
4 48-4
DOI
出版ステータスPublished - 2003 10月 1
外部発表はい

ASJC Scopus subject areas

  • 生理学
  • 肝臓学
  • 消化器病学
  • 生理学(医学)

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