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  • Title: Ameliorating effect of anti-Fas ligand MAb on wasting disease in murine model of chronic colitis.
    Author: Dan N, Kanai T, Totsuka T, Iiyama R, Yamazaki M, Sawada T, Miyata T, Yagita H, Okumura K, Watanabe M.
    Journal: Am J Physiol Gastrointest Liver Physiol; 2003 Oct; 285(4):G754-60. PubMed ID: 12969829.
    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+CD45RBhigh 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-gamma production by anti-CD3/CD28-stimulated lamina propria CD4+ T cells but suppressed TNF-alpha and IL-1beta 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.
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