Journal
FASEB JOURNAL
Volume 14, Issue 11, Pages 1471-1484Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.14.11.1471
Keywords
bacteria; chemokine; transcription; NF-kappa B
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Enteropathogenic Yersinia bacteria trigger the production of the proinflammatory chemokine IL-8, an important chemokine for the recruitment of polymorphonuclear leukocytes (PMN). Yersinia is resistant to phagocytosis by PMN, and the recruitment of these cells is thought to be part of a pathogenic strategy of Yersinia to establish infection by allowing the pathogen to gain access to, and disseminate within, host tissue. We report here that Yersinia expressing the outer membrane protein invasin triggers IL-8 production in epithelial cells. The 195 carboxyl-terminal amino acids of invasin when linked to latex beads are sufficient to trigger IL-8 production. By means of IL-8 promoter reporter gene assays and electrophoretic mobility shift assay experiments, the minimal optimal region of the IL-8 promoter responsive to invasin was identified and invasin-responsive control elements were characterized. Invasin-induced activation of the IL-8 promoter tvas found to be mediated through a previously identified NF-kappa B element. This NF-kappa B binding site preferentially binds Rel p65-p65 homodimers as well as some p50-p65 heterodimers in response to stimulation by invasin. Invasin-induced NF-kappa B activation col-related with degradation of I kappa B alpha. and the inhibition of NF-kappa B by specific inhibitors of I kappa B activation blocked invasin-induced IL-8 secretion. Invasin-triggered IL-8 production does not depend on invasin-triggered uptake of bacteria, and is independent of a functional PI3-kinase. This report is the first to demonstrate the molecular basis of IL-8 production triggered by enteropathogenic bacteria. Together, these data elucidate the possible early pathomechanisms operating in Yersinia infection and may have implications for the design of novel therapeutics directed against this enteropathogen.
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