How bacteria-induced apoptosis of intestinal epithelial cells contributes to mucosal inflammation.
How bacteria-induced apoptosis of intestinal epithelial cells contributes to mucosal inflammation.
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DOI：
10.4061/2010/574568
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发表时间：
2010-07-06
影响因子：
2
通讯作者：
Hausmann M
中科院分区：
文献类型：
--
作者：
Hausmann M
肠上皮细胞的生命周期通过细胞凋亡和/或细胞脱落而终止。完整肠粘膜上皮细胞的凋亡缺失并不伴随可检测到的炎症反应或屏障功能的丧失。但据报道，患有炎症性肠病的患者上皮屏障的通透性增加，上皮细胞凋亡率增加。微生物群可以诱导或抑制肠上皮细胞凋亡，从而分别导致粘膜炎症或支持上皮完整性。细菌介导的细胞因子分泌和细胞信号传导的改变是上皮损伤的核心。暴露于侵入性细菌后分泌的肿瘤坏死因子（TNF）会诱导细胞凋亡和细胞脱落。 TNF是转录因子核因子κB的主要靶基因，具有促凋亡和抗凋亡作用。自噬促进细胞存活和“自噬”细胞死亡。如果自噬针对微生物，则称为异体自噬。抑制异体吞噬已被证明会降低细胞存活率。内质网 (ER) 应激导致错误折叠的蛋白质在 ER 腔中积聚。有人提出，内质网应激和自噬可能在肠上皮细胞内相互作用。宿主很好地提出了响应感染的细胞凋亡，以消除受感染的上皮细胞，或者可能是微生物病原体从耗尽的细胞中逃逸以侵入更深的粘膜层以实现长期细菌定植的策略。
The life cycle of an intestinal epithelial cell is terminated by apoptosis and/or cell shedding. Apoptotic deletion of epithelial cells from the intact intestinal mucosa is not accompanied by detectable inflammatory response or loss of barrier function. But increased permeability of the epithelial barrier and increased apoptotic rates of epithelial cells have been reported for patients suffering from inflammatory bowel disease. Microbiota can both induce or inhibit apoptosis of intestinal epithelial cells thus contribute to mucosal inflammation or support epithelial integrity respectively. Bacteria-mediated cytokine secretion and altered cell signalling are central to epithelial injury. Tumor necrosis factor (TNF) secreted after exposure to invasive bacteria induces both apoptosis and cell shedding. TNF is the major target gene of the transcription factor nuclear factor-kappa B with both pro- and anti-apoptotic effects. Autophagy promotes both cell survival and “autophagic” cell death. If autophagy is directed against microbes it is termed xenophagy. Inhibition of xenophagy has been shown to decrease cell survival. Endoplasmic reticulum (ER) stress causes misfolded proteins to accumulate in the ER lumen. It was suggested that ER stress and autophagy may interact within intestinal epithelial cells. Apoptosis in response to infection may be well proposed by the host to delete infected epithelial cells or could be a strategy of microbial pathogens to escape from exhausted cells to invade deeper mucosal layers for a prolonged bacterial colonization.