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

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12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)G754-G760
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume285
Issue number4 48-4
DOIs
Publication statusPublished - 2003 Oct 1
Externally publishedYes

Keywords

  • Crohn's disease
  • Fas/FasL
  • Murine model
  • Therapy

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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    Dan, N., Kanai, T., Totsuka, T., Iiyama, R., Yamazaki, M., Sawada, T., Miyata, T., Yagita, H., Okumura, K., & Watanabe, M. (2003). Ameliorating effect of anti-Fas ligand MAb on wasting disease in murine model of chronic colitis. American Journal of Physiology - Gastrointestinal and Liver Physiology, 285(4 48-4), G754-G760. https://doi.org/10.1152/ajpgi.00071.2003