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

Salmonella-epithelial cell interactions are known to activate the proinflammatory 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 crosstalk 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 PhoP(c), 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, I kappa B alpha protein 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.