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Infect. Immun. doi:10.1128/IAI.01317-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Campylobacter-induced interleukin-8 secretion in polarized human intestinal epithelial cells requires Campylobacter-secreted CDT and TLR-mediated activation of NF-B

Department of Nutrition & Food Science, Department of Cell Biology & Molecular Genetics, University of Maryland, College Park, MD 20742; Center for Veterinary Medicine, Office of Research, Food & Drug Administration, Laurel, MD 20708

^* To whom correspondence should be addressed. Email: wenxsong{at}umd.edu.

	Abstract

Campylobacter jejuni/coli colonize and infect the intestinal epithelium and cause acute inflammatory diarrhea. The intestinal epithelium serves as a physical barrier and a sensor to bacterial infection by secreting proinflammatory cytokines. This study examined the mechanisms for Campylobacter-induced proinflammatory chemokine interleukin (IL)-8 secretion using polarized human colonic epithelial cells T84 as a model. C. jejuni increased the secretion of both IL-8 and TNF- in polarized epithelial cells. However, the increase in IL-8 secretion was independent of Campylobacter-stimulated TNF- secretion. Polarized T84 cells secreted IL-8 predominantly to the basolateral medium independently of inoculation directions. While there was a significant correlation between the IL-8 secreting levels and Campylobacter invasion, all 11 tested strains increased IL-8 secretion by polarized T84 cells despite their differences in adherence, invasion, and transcytosis efficiencies. Cell free supernatants of Campylobacter-T84 culture increased IL-8 secretion to levels similar to that induced by live bacterial inoculation. The IL-8 induction ability of the supernatant was reduced by flagellum and cytolethal distending toxin (CDT) gene mutants, treatment of the supernatant with protease K and heat, and treatment of T84 cells with Toll like receptor (TLR) inhibitors, MyD88 inhibitory peptide and chloroquine. NF-B inhibitors or cdtB mutation plus MyD88 inhibitor, but not flaA and cdtB double mutations, abolished the ability of the supernatant to induce IL-8 secretion. Taken together, our results demonstrate that Campylobacter-induced IL-8 secretion requires functional flagellum and CDT and depends on the activation of NF-B through TLR signaling and CDT in human intestine epithelial cells.