부산대학교 도서관

The mucosal lining of the human intestine is constantly bathed in a milieu of commensal gut flora, the vast majority of these being nonpathogenic microorganisms. Here, we demonstrate that microbial-epithelial cell interactions not only affect proinflammatory pathways but also influence [beta]-catenin signaling, a key component in regulating epithelial cell proliferation. The nonpathogenic Salmonella strain PhoPc activates the [beta]-catenin signaling pathway of human epithelia via a blockade of [beta]-catenin degradation. Normal [beta]-catenin ubiquitination necessary for constitutive [beta]-catenin degradation is abolished, allowing the accumulation and translocation of [beta]-catenin to the nucleus. Transcriptional activation mediated by the [beta]-catenin/T cell factor complex increases c-myc expression and enhances cell proliferation. We also show that the Salmonella effector protein AvrA is involved in modulating this [beta]-catenin activation. These data suggest that nonvirulent bacterial-epithelial interactions can influence [beta]-catenin signaling and cell growth control in a manner previously unsuspected. host defense; inflammation; cellular proliferaton