Wingless homolog Wnt11 suppresses bacterial invasion and inflammation in intestinal epithelial cells
Wingless homolog Wnt11 suppresses bacterial invasion and inflammation in intestinal epithelial cells
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DOI：
10.1152/ajpgi.00080.2011
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发表时间：
2011-12-01
影响因子：
4.5
通讯作者：
Sun, Jun
中科院分区：
文献类型：
--
作者：
Liu, Xingyin;Wu, Shaoping;Sun, Jun
Liu X，Wu S，Xia Y，Li XE，Xia Y，Zhou ZD，Sun J. Wingless homolog Wnt 11 suppresses bacterial invasion and inflammation in intestinal epithelial cells.美国生理学杂志胃肠和肝脏生理学301：G992-G1003，2011年。首次发表于2011年9月8日; doi：10.1152/ajpgi.00080.2011。Wnt 11在胃肠道上皮细胞增殖中起着重要作用，以前的研究主要集中在发育和免疫反应上。然而，肠道细菌如何调节Wnt 11以及Wnt 11如何调节宿主对病原菌的反应的作用仍然未被探索。本研究探讨了沙门氏菌感染对肠上皮细胞Wnt激活的影响。我们发现沙门氏菌定植后Wnt 11 mRNA和蛋白表达升高。细菌感染后，上皮细胞中的Wnt 11蛋白分泌也升高。此外，我们证明了致病性沙门氏菌调节Wnt 11在体内的表达和定位。我们发现与正常Wnt 11水平的细胞相比，Wnt 11过表达的细胞中沙门氏菌的侵袭减少。IL-8 mRNA在Wnt 11转染细胞中是低的，然而，它在Wnt 11表达水平低的细胞中增强。在功能上，Wnt 11过表达抑制沙门氏菌诱导的细胞凋亡。AvrA是一种已知的细菌效应蛋白，其稳定Wnt信号传导的下游调节物β-连环蛋白，并抑制细菌诱导的肠道炎症。我们观察到Wnt 11的表达，分泌和转录活性由沙门氏菌AvrA调节。总的来说，Wnt 11通过阻断病原菌的入侵、抑制炎症和抑制细胞凋亡来参与保护宿主肠细胞。Wnt 11是一种新型的肠道内稳态和宿主防御的重要贡献者。
Liu X, Wu S, Xia Y, Li XE, Xia Y, Zhou ZD, Sun J. Wingless homolog Wnt11 suppresses bacterial invasion and inflammation in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 301: G992-G1003, 2011. First published September 8, 2011; doi:10.1152/ajpgi.00080.2011.-Wnt11 plays an essential role in gastrointestinal epithelial proliferation, and previous investigations have focused on development and immune responses. However, the roles of how enteric bacteria regulate Wnt11 and how Wnt11 modulates the host response to pathogenic bacteria remain unexplored. This study investigated the effects of Salmonella infection on Wnt activation in intestinal epithelial cells. We found that Wnt11 mRNA and protein expression were elevated after Salmonella colonization. Wnt11 protein secretion in epithelial cells was also elevated after bacterial infection. Furthermore, we demonstrated that pathogenic Salmonella regulated Wnt11 expression and localization in vivo. We found a decrease in Salmonella invasion in cells with Wnt11 overexpression compared with cells with normal Wnt11 level. IL-8 mRNA in Wnt11-transfected cells was low; however, it was enhanced in cells with a low level of Wnt11 expression. Functionally, Wnt11 overexpression inhibited Salmonella-induced apoptosis. AvrA is a known bacterial effector protein that stabilizes beta-catenin, the downstream regulator of Wnt signaling, and inhibits bacterially induced intestinal inflammation. We observed that Wnt11 expression, secretion, and transcriptional activity were regulated by Salmonella AvrA. Overall, Wnt11 is involved in the protection of the host intestinal cells by blocking the invasion of pathogenic bacteria, suppressing inflammation, and inhibiting apoptosis. Wnt11 is a novel and important contributor to intestinal homeostasis and host defense.