Submitted on November 16, 2004
Accepted on March 8, 2005
Crosstalk between NF-
B and 
-catenin pathways in bacterial-colonized intestinal epithelial cells
Jun Sun1*, Michael E. Hobert1, Yingli Duan1, Anjali S. Rao1, Tong-Chuan He2, Eugene B. Chang3, and James L. Madara1
1 Department of Pathology, The University of Chicago, Chicago, IL, USA
2 Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL, USA
3 The Inflammatory Bowel Disease Research Center, Department of Medicine, The University of Chicago, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: jsun{at}bsd.uchicago.edu.
Salmonella-epithelial cell interactions are known to activate the pro-inflammatory
Nuclear Factor Kappa B (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 cross-talk
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 PhoPc, 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, Inhibitor of Kappa B-
protein (IB)
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.
