Autophagy in the intestinal epithelium reduces endotoxin-induced inflammatory responses by inhibiting NF-κB activation
Autophagy in the intestinal epithelium reduces endotoxin-induced inflammatory responses by inhibiting NF-κB activation
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DOI：
10.1016/j.abb.2010.12.009
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发表时间：
2011-02-15
影响因子：
3.9
通讯作者：
Yoshida, Masaru
中科院分区：
文献类型：
--
作者：
Fujishima, Yoshimi;Nishiumi, Shin;Yoshida, Masaru
自噬是一种溶酶体降解途径，对于生存、分化、发育和稳态至关重要。越来越多的证据表明，自噬受损会导致多种疾病的发病机制。然而，尽管之前的研究已经指出自噬与肠道炎症之间的关系，但自噬在肠上皮中的作用尚不清楚。在这项研究中，我们研究了肠上皮自噬与炎症反应的关系。我们生成了在肠上皮中条件性删除 Atg7 的小鼠，Atg7 是自噬调节基因之一。在Atg7缺陷的小肠上皮中，与对照小肠组织相比，LPS诱导的TNF-α和IL-1βmRNA的产生增强。此外，在 Atg7 缺陷的肠上皮中，LPS 诱导的 NF-κ B 激活程度得到促进。这些结果表明，自噬可以减弱内毒素诱导的肠上皮炎症反应，从而维持肠道稳态。 (C) 2010 Elsevier Inc. 保留所有权利。
Autophagy is a lysosomal degradation pathway that is essential for survival, differentiation, development and homeostasis. There is growing evidence that impaired autophagy leads to the pathogenesis of diverse diseases. However, the role of autophagy in intestinal epithelium is not clearly understood, although previous studies have pointed out the possibility for the relationships of autophagy with bowel inflammation. In this study, we investigated the involvement of autophagy in intestinal epithelium with inflammatory responses. We generated the mice with a conditional deletion of Atg7, which is one of the autophagy regulated gene, in intestinal epithelium. In Atg7-deficient small intestinal epithelium, LPS-induced production of TNF-alpha and IL-1 beta mRNA was enhanced in comparison to the control small intestinal tissues. In addition, the degree of LPS-induced activation of NF-kappa B was promoted in Atg7-deficient intestinal epithelium. These results demonstrate that autophagy can attenuate endotoxin-induced inflammatory responses in intestinal epithelium resulting in the maintenance of intestinal homeostasis. (C) 2010 Elsevier Inc. All rights reserved.