title: Wingless homolog Wnt11 suppresses bacterial invasion and inflammation in intestinal epithelial cells.
abstract: 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 β-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.
authors: Gastroenterology & Hepatology Division, Department of Medicine, University of Rochester, Rochester, New York 14642, USA.
authors: Xingyin
authors: X
authors: Liu
authors: Shaoping
authors: S
authors: Wu
authors: Yinglin
authors: Y
authors: Xia
authors: Xi Emma
authors: XE
authors: Li
authors: Yuxuan
authors: Y
authors: Xia
authors: Zhongren David
authors: ZD
authors: Zhou
authors: Jun
authors: J
authors: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D018938:Caco-2 Cells; D003106:Colon / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D012480:Salmonella Infections / Q000276:immunology* / Q000473:pathology; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D051153:Wnt Proteins / Q000235:genetics / Q000276:immunology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C487891:AvrA protein, Salmonella typhimurium; D001426:Bacterial Proteins; D051153:Wnt Proteins; C540523:Wnt11 protein, human; C508957:Wnt11 protein, mouse; D051176:beta Catenin