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Am J Physiol Gastrointest Liver Physiol (March 24, 2005). doi:10.1152/ajpgi.00515.2004
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Submitted on November 16, 2004
Accepted on March 8, 2005

Crosstalk between NF-{kappa}B and {beta}-catenin pathways in bacterial-colonized intestinal epithelial cells

Jun Sun1*, Michael E. Hobert1, Yingli Duan1, Anjali S. Rao1, Tong-Chuan He2, Eugene B. Chang3, and James L. Madara1

1 Department of Pathology, The University of Chicago, Chicago, IL, USA
2 Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL, USA
3 The Inflammatory Bowel Disease Research Center, Department of Medicine, The University of Chicago, Chicago, IL, USA

* To whom correspondence should be addressed. E-mail: jsun{at}bsd.uchicago.edu.

Salmonella-epithelial cell interactions are known to activate the pro-inflammatory Nuclear Factor Kappa B (NF-{kappa}B) signaling pathway and have recently been found to also influence the {beta}-catenin signaling pathway, an important regulator of epithelial cell proliferation and differentiation. Here, using polarized epithelial cell models, we demonstrate that these same bacteria-mediated effects also direct the molecular cross-talk between the NF-{kappa}B and {beta}-catenin signaling pathways. Convergence of these two pathways is a result of the direct interaction between the NF-{kappa}B p50 subunit and {beta}- catenin. We show that PhoPc, the avirulent derivative of a wild-type Salmonella strain, attenuates NF-{kappa}B activity by stabilizing the association of {beta}-catenin with NF-{kappa}B. In cell lines expressing constitutively active {beta}-catenin, Inhibitor of Kappa B-{alpha} protein (I{kappa}B{alpha}) was indirectly stabilized and NF-{kappa}B activity was repressed after wild-type Salmonella colonization. Accordingly, constitutively active {beta}-catenin was found to inhibit the secretion of IL-8. Thus, our findings strongly suggest that the crosstalk between the {beta}- catenin and NF-{kappa}B signaling pathways is an important regulator of intestinal inflammation.




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