Nuclear Factor-kappa B Activation and Chemokine Genes Expression in HT-29 Intestinal Epithelial Cells in Response to Clostridium difficile Toxin A Stimulation

ABSTRACT

Intestinal epithelial cells are known to up-regulate the expression of several chemokines in response to bacterial toxins. Since there has been little understanding on the cellular mechanisms of C. difficile toxin A-induced mucosal inflammation, we investigated whether nuclear factor-kappa B (NF-kappaB) could regulate chemokine gene expression in HT-29 intestinal epithelial cells stimulated with C. difficile toxin A. C. difficile toxin A rapidly increased signals of NF-kappaB composed with p65 and p50 subunits in HT-29 cells, whereas it decreased the signals of IkappaBalpha. Blocking the NF-kB activation by transfection with dominant negative I kappa B alpha-containing retrovirus attenuated the upregulated expression of IL-8, GRO-alpha, and MCP-1 induced by C. difficile toxin A. These results suggest that NF-kappaB is a major regulator of chemokine gene expression in C. difficile toxin A-stimulated intestinal epithelial cells.