ACTIVATION OF NF-KAPPA-B IN INTESTINAL EPITHELIAL-CELLS BY ENTEROPATHOGENIC ESCHERICHIA-COLI

The initial response to infection is recruitment of acute inflammatory cells to the involved site. Interleukin (IL)-8 is the prototypical ef fector molecule for this process. Transcription of the IL-8 gene is pr imarily governed by the nuclear transcription factor (NF)-kappa B. Int estinal epithelial cells produce IL-8 in response to infection by ente ric pathogens yet remain quiescent in a milieu where they are literall y bathed in normal bacterial flora. We therefore sought to investigate NF-kappa B activation in response to enteropathogenic Escherichia col i (EPEC), nonpathogenic E, coli, and bacterial lipopolysaccharide in a n intestinal epithelial cell (T84) model and to determine whether EPEC -induced activation of NF-kappa B factor is causally linked to IL-8 pr oduction. We report herein that NF-kappa B is activated by EPEC, yet s uch a response is not extended to nonpathogenic organisms or purified E. coli lipopolysaccharide. Transcription factor decoys significantly diminished IL-8 production in response to EPEC, demonstrating a causal relationship. Furthermore, deletion of specific EPEC virulence genes abrogates the NF-kappa B-activating property of this pathogen, suggest ing that specific bacterial factors are crucial for inducing this resp onse. These studies show for the first;time that infection of intestin al epithelial cells with EPEC activates NF-kappa B, which in turn init iates IL-8 transcription, and highlight the differential response of t hese cells to bacterial pathogens vs. nonpathogens.