Fas ligand down-regulates cytokine-induced fas receptor expression on insulinoma (NIT-1), but not islet cells, from autoimmune nonobese diabetic mice

Augstein, P; Heinke, P; Salzsieder, E; Berg, S; Rettig, R; Salzsieder, C; Harrison, LC

Author(s): Augstein, P; Heinke, P; Salzsieder, E; Berg, S; Rettig, R; Salzsieder, C; Harrison, LC;
Details: Publication Year 2004-06,Volume 145,Issue #6,Page 2747-2752
Journal Title: ENDOCRINOLOGY
Publication Type: Journal Article
Abstract: In the pathogenesis of autoimmune type 1 diabetes, the apoptosis receptor Fas appears de novo on the surface of insulin-producing beta-cells. Fas expression is thought to be induced by proinflammatory cytokines, such as IL-1beta, interferon-gamma (IFNgamma), and TNFalpha, released by islet-infiltrating mononuclear cells. To determine whether beta-cells can modulate their sensitivity to apoptosis at the level of Fas, we investigated the effect of Fas ligand (FasL) on surface expression of Fas in NIT-1 insulinoma cells from nonobese diabetic (NOD) mice prone to autoimmune diabetes and islet cells from NOD and nonautoimmune BALB/c mice. In NIT-1 insulinoma cells, Fas expression induced by the cytokine combination IL-1beta and IFNgamma was reduced in the presence of FasL, whereas in islet cells Fas expression was unaffected by FasL. The effect of FasL on NIT-1 cells was evident during and after the induction of Fas expression by IL-1beta and IFNgamma. Thus, FasL down-regulates cytokine-induced Fas expression in NOD mouse-derived NIT-1 cells, but not in NOD or BALB/c mouse islets. The ability of NIT-1 cells to down-regulate Fas receptor in response to ligation is similar to that of a variety of tumor cells, which may use this mechanism to escape destruction by cytotoxic T cells. Islets apparently cannot protect themselves against FasL-induced apoptosis by down-regulating the Fas receptor. Understanding how NIT-1 insulinoma cells down-regulate Fas receptor in response to ligation by FasL, has therapeutic implications for protecting normal beta-cells in autoimmune type 1 diabetes.
Publisher: ENDOCRINE SOC
Keywords: PANCREATIC BETA-CELLS; UP-REGULATION; NOD MICE; T-CELL; APOPTOSIS; DEATH; CD95; DESTRUCTION; SURFACE; MECHANISMS
Publisher's Version: https://doi.org/10.1210/en.2003-0754
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2004-06-01 12:00:00