Crosstalk between NF-kappaB and beta-catenin pathways in bacterial-colonized intestinal epithelial cells.
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.
Sun
Jun
J
Department of Pathology, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA. jsun@bsd.uchicago.edu
Hobert
Michael E
ME
Duan
Yingli
Y
Rao
Anjali S
AS
He
Tong-Chuan
TC
Chang
Eugene B
EB
Madara
James L
JL
D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D045325:HCT116 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D012480:Salmonella Infections / Q000378:metabolism*; D012486:Salmonella typhimurium; D015398:Signal Transduction / Q000502:physiology; D047990:TNF Receptor-Associated Factor 1 / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin; D019014:fas Receptor / Q000378:metabolism
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D047990:TNF Receptor-Associated Factor 1; D015534:Trans-Activators; D051176:beta Catenin; D019014:fas Receptor; D000072000:NF-KappaB Inhibitor alpha