Wnt2 inhibits enteric bacterial-induced inflammation in intestinal epithelial cells.
Wnt2 inhibits enteric bacterial-induced inflammation in intestinal epithelial cells.
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DOI：
10.1002/ibd.21788
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发表时间：
2012-03
影响因子：
4.9
通讯作者：
Sun, Jun
中科院分区：
文献类型：
--
作者：
Liu, Xingyin;Lu, Rong;Wu, Shaoping;Zhang, Yong-guo;Xia, Yinglin;Sartor, R. Balfour;Sun, Jun
Wnt信号在胃肠道上皮细胞增殖中起重要作用。大多数研究集中在发育和免疫反应。细菌感染可以是慢性的，并增加炎症性肠病和结肠炎相关癌症的风险。然而，我们缺乏关于细菌如何调节Wnt蛋白以及Wnt如何调节宿主对肠道细菌的反应的研究。本研究探讨了沙门氏菌和大肠杆菌的作用。大肠杆菌对肠上皮细胞中Wnt家族成员之一Wnt 2的作用。使用培养的上皮细胞，沙门氏菌结肠炎小鼠模型，和gnotobiotic小鼠模型，我们发现，Wnt 2的mRNA和蛋白质的表达水平升高后，细菌感染。肠道细菌调节Wnt 2在肠道中的位置。此外，我们发现Wnt 2的升高是通过抑制细胞凋亡和对感染的炎症反应来进行宿主防御的策略。使用Wnt 2 siRNA分析，我们显示上皮细胞中炎性细胞因子IL-8增强。过表达Wnt 2的细胞具有较少的细菌诱导的IL-8分泌。AvrA是一种细菌蛋白，通过稳定Wnt的下游靶标β-连环蛋白来抑制炎症。我们发现Wnt 2的稳定性是通过泛素化来调节的。此外，沙门氏菌和大肠杆菌的细菌蛋白AvrA。coli中稳定Wnt 2蛋白的体内表达。在一个前无菌系统中，E.大肠杆菌F18表达AvrA后，Wnt 2的表达量增加，并改变了Wnt 2在肠道中的分布。Wnt 2有助于响应肠道细菌的宿主保护。因此，我们的研究结果揭示了Wnt在宿主-病原体相互作用和炎症中的先前未定义的作用。
Wnt signaling plays an essential role in gastrointestinal epithelial proliferation. Most investigations have focused on developmental and immune responses. Bacterial infection can be chronic and increases the risk of inflammatory bowel disease and colitis-associated cancer. However, we lack studies on how bacteria regulate Wnt proteins and how Wnts modulate the host responses to enteric bacteria. This study investigated the effects of Salmonella and E. coli on Wnt2, one of the Wnt family members, in intestinal epithelia cells. Using cultured epithelial cells, a Salmonella-colitis mouse model, and a gnotobiotic mouse model, we found that Wnt2 mRNA and protein expression levels were elevated after bacterial infection. Enteric bacteria regulate Wnt2 location in the intestine. Furthermore, we found that elevation of Wnt2 was a strategy for host defense by inhibiting cell apoptosis and inflammatory responses to infection. Using Wnt2 siRNA analysis, we show enhanced inflammatory cytokine IL-8 in epithelial cells. Cells over-expressed Wnt2 had less bacterial-induced IL-8 secretion. AvrA is a bacterial protein that inhibits inflammation by stabilizing beta-catenin, the down-stream target of Wnt. We found that the stabilization of Wnt2 was regulated through ubiquitination. Moreover, the bacterial protein AvrA from Salmonella and E. coli stabilized Wnt2 protein expression in vivo. In an ex-germ-free system, E. coli F18 expressing AvrA increased Wnt2 expression and changed Wnt2 distribution in intestine. Wnt2 contributes to host protection in response to enteric bacteria. Our findings thus reveal a previously undefined role of Wnt for host-pathogen interaction and inflammation.
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影响因子：
29.4
作者：
Gradel, Kim O.;Nielsen, Hans L.;Nielsen, Henrik
通讯作者：
Nielsen, Henrik
影响因子：
3.2
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MILLER, SI;MEKALANOS, JJ
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MEKALANOS, JJ
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Naumann M
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3.1
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Hardt, WD
影响因子：
3.7
作者：
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通讯作者：
Jobin, Christian