Caspases-3,-8, and-9 are required for induction of epithelial cell apoptosis by enteropathogenic E-coli but are dispensable for increased paracellular permeability
Caspases-3,-8, and-9 are required for induction of epithelial cell apoptosis by enteropathogenic E-coli but are dispensable for increased paracellular permeability
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DOI：
10.1016/j.micpath.2007.10.007
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发表时间：
2008-04-01
影响因子：
3.8
通讯作者：
Buret, Andre G.
中科院分区：
文献类型：
--
作者：
Flynn, Andrew N.;Buret, Andre G.
肠致病性大肠杆菌（EPEC）是腹泻的重要原因，特别是在发展中国家的婴儿中。由于EPEC感染引起的肠道通透性增加被认为是腹泻发展的一个因素。肠上皮细胞的程序性细胞死亡（凋亡）水平异常高可导致肠通透性增加。EPEC对细胞凋亡的影响仍不完全清楚。本研究的特点是EPEC诱导上皮细胞凋亡的机制，并检查这种影响是否有助于提高渗透性在体外感染模型。我们报道了EPEC诱导T84肠上皮细胞凋亡的机制，包括半胱天冬酶-3、-6、-8和-9、PARP裂解和溶酶体形成。此外，EPEC时间依赖性地增加细胞旁渗透性，如通过跨上皮阻力和3000 MW葡聚糖的顶侧至基底侧运动所评估的。此外，EPEC感染导致紧密连接ZO-1和occludin的切割和错误定位。然而，半胱天冬酶的药理学抑制并不能阻止EPEC诱导的上皮屏障结构和功能的破坏。总之，这些结果表明，在EPEC感染过程中，上皮细胞凋亡的半胱天冬酶依赖性上调与肠屏障功能受损无关。皇冠版权所有（C）2007由爱思唯尔有限公司出版。保留所有权利。
Enteropathogenic Escherichia coli (EPEC) is an important cause of diarrhea, particularly among infants in developing countries. An increase in intestinal permeability due to EPEC infection has been suggested as a factor in the development of diarrhea. Abnormally high levels of programmed cell death (apoptosis) of intestinal epithelial cells can lead to increased intestinal permeability. The effects of EPEC on cell apoptosis remain incompletely understood. This study characterized the mechanisms of EPEC-induced epithelial apoptosis and examined whether this effect contributes to heightened permeability in an in vitro model of infection. We report that EPEC-induced apoptosis in T84 intestinal epithelial cells via a mechanism involving caspases-3, -6, -8, and -9, the cleavage of PARP, and oligonucleosome formation. In addition, EPEC time-dependently increased paracellular permeability as assessed by transepithelial resistance and the apical-to-basolateral movement of 3000 MW dextran. Furthermore, EPEC infection led to the cleavage and mislocalization of tight junctional ZO-1 and occludin. However, pharmacological inhibition of caspases did not prevent the EPEC-induced disruptions in epithelial barrier structure and function. Taken together, these results suggest that a caspase-dependent Upregulation in epithelial cell apoptosis during EPEC infection occurs independent of impaired intestinal barrier function. Crown Copyright (C) 2007 Published by Elsevier Ltd. All rights reserved.