Oxidative stress induces the expression of Fas and Fas ligand and apoptosis in murine intestinal epithelial cells
Oxidative stress induces the expression of Fas and Fas ligand and apoptosis in murine intestinal epithelial cells
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DOI：
10.1016/s0891-5849(02)01141-3
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发表时间：
2002-12-15
影响因子：
7.4
通讯作者：
Ernst, PB
中科院分区：
文献类型：
--
作者：
Denning, TL;Takaishi, H;Ernst, PB
肠道上皮细胞的功能受到局部免疫和炎症反应的影响。在这项研究中，我们研究了肠上皮细胞损伤发生在激活的炎症细胞存在的可能性，如中性粒细胞和巨噬细胞，通过产生活性氧物种(ROS)。暴露于50~150 MU H_2O_2后，肠上皮细胞Fas及Fas-L基因和蛋白表达水平均升高，肠上皮细胞发生凋亡。用激动型抗Fas抗体处理H_2O_2暴露的细胞，而不用同型对照抗体处理，可显著促进细胞凋亡。细胞凋亡与半胱氨酸天冬氨酸蛋白酶8的激活有关，而半胱氨酸天冬氨酸蛋白酶8的抑制剂Z-IETD可阻断过氧化氢诱导的肠上皮细胞凋亡。因此，ROS诱导Fas和Fas-L的表达与肠上皮细胞的凋亡有关。这些数据支持这样的假设，即在暴露于氧化应激之后，肠细胞通过Fas介导的途径为细胞死亡做好准备。(C)2002年爱思唯尔科学公司。
Intestinal epithelial cell function is compromised by local immune and inflammatory responses. In this study, we examined the possibility that intestinal epithelial cell injury occurs in the presence of activated inflammatory cells, such as neutrophils and macrophages, via production of reactive oxygen species (ROS). Following exposure to 50-150 muM H2O2, levels of mRNA and protein for Fas and, to a lesser degree, Fas-L were increased and intestinal epithelial cells underwent apoptosis. Treatment of H2O2-exposed cells with agonistic anti-Fas antibody, but not isotype control antibody, significantly enhanced apoptosis. Apoptosis was associated with the activation of caspase 8, while Z-IETD, an inhibitor of caspase 8, blocked apoptosis of H2O2-exposed intestinal epithelial cells. Thus, ROS induced Fas and Fas-L expression in association with intestinal epithelial cell apoptosis. These data support the hypothesis that, following exposure to oxidative stress, enterocytes are primed for cell death via Fas-mediated pathways. (C) 2002 Elsevier Science Inc.