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Inflamm Bowel Dis. 2012 Mar;18(3):418-29. doi: 10.1002/ibd.21788. Epub 2011 Jun 14.

Wnt2 inhibits enteric bacterial-induced inflammation in intestinal epithelial cells.

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  • 1Gastroenterology & Hepatology Division, Department of Medicine, University of Rochester, Rochester, New York, North Carolina, USA.

Abstract

BACKGROUND:

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 Escherichia coli on Wnt2, one of the Wnt family members, in intestinal epithelia cells.

METHODS:

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.

RESULTS:

Using Wnt2 siRNA analysis, we show enhanced inflammatory cytokine IL-8 in epithelial cells. Cells overexpressed Wnt2 had less bacterial-induced IL-8 secretion. AvrA is a bacterial protein that inhibits inflammation by stabilizing β-catenin, the downstream 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.

CONCLUSIONS:

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.

Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

PMID:
21674728
[PubMed - indexed for MEDLINE]
PMCID:
PMC3294455
Free PMC Article
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