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This Article Full Text Full Text (PDF) All Versions of this Article: 289/1/G129    most recent 00515.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Sun, J. Articles by Madara, J. L. Search for Related Content PubMed PubMed Citation Articles by Sun, J. Articles by Madara, J. L.

INFLAMMATION/IMMUNITY/MEDIATORS

Crosstalk between NF-B and -catenin pathways in bacterial-colonized intestinal epithelial cells

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

Submitted 16 November 2004 ; accepted in final form 8 March 2005

Salmonella-epithelial cell interactions are known to activate the proinflammatory NF-B signaling pathway and have recently been found to also influence the -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 crosstalk between the NF-B and -catenin signaling pathways. Convergence of these two pathways is a result of the direct interaction between the NF-B p50 subunit and -catenin. We show that PhoP^c, the avirulent derivative of a wild-type Salmonella strain, attenuates NF-B activity by stabilizing the association of -catenin with NF-B. In cell lines expressing constitutively active -catenin, IB protein was indirectly stabilized and NF-B activity was repressed after wild-type Salmonella colonization. Accordingly, constitutively active -catenin was found to inhibit the secretion of IL-8. Thus our findings strongly suggest that the crosstalk between the -catenin and NF-B signaling pathways is an important regulator of intestinal inflammation.

bacteria; inflammation; nuclear factor-B; interleukin-8