Salmonella Research Today is a free monthly online journal that collates and summarizes the latest research about Salmonella, including details on salmonella typhimurium, food poisoning, infection, treatment.

Crosstalk between NF-kappaB and beta-catenin pathways in bacterial-colonized intestinal epithelial cells.

Sun J, Hobert ME, Duan Y, Rao AS, He TC, Chang EB, Madara JL

Department of Pathology, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA. jsun@bsd.uchicago.edu

Salmonella-epithelial cell interactions are known to activate the proinflammatory NF-kappaB 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 crosstalk between the NF-kappaB and beta-catenin signaling pathways. Convergence of these two pathways is a result of the direct interaction between the NF-kappaB p50 subunit and beta-catenin. We show that PhoP(c), the avirulent derivative of a wild-type Salmonella strain, attenuates NF-kappaB activity by stabilizing the association of beta-catenin with NF-kappaB. In cell lines expressing constitutively active beta-catenin, IkappaBalpha protein was indirectly stabilized and NF-kappaB 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-kappaB signaling pathways is an important regulator of intestinal inflammation.

Published 17 June 2005 in Am J Physiol Gastrointest Liver Physiol, 289(1): G129-37.
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