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