Campylobacter jejuni cytolethal distending toxin mediates release of interleukin-8 from intestinal epithelial cells

Live cells of Campylobacter jejuni and Campylobacter coli can induce releas e of interleukin-8 (IL-8) from INT407 cells. Additionally, membrane fractio ns of C. jejuni 81-176, but not membrane fractions of C, coli strains, can also induce release of IL-8, Membrane preparations from 81-176 mutants defe ctive in any of the three membrane-associated protein subunits of cytoletha l distending toxin (CDT) were unable to induce IL-8, The presence of the th ree cdf genes on a shuttle plasmid in trans restored both CDT activity and the ability to release IL-8 to membrane fractions. However, CDT mutations d id not affect the ability of 81-176 to induce IL-8 during adherence to or i nvasion of INT407 cells, When C. jejuni cdt genes were transferred on a shu ttle plasmid into a C, coli strain lacking CDT, membrane preparations becam e positive in both CDT and IL-8 assays. Growth of C,jejuni in physiological levels of sodium deoxycholate released all three CDT proteins, as well as CDT activity and IL-8 activity, from membranes into supernatants. Antibodie s against recombinant forms of each of the three CDT subunit proteins neutr alized both CDT activity and the activity responsible far IL-8 release, The data suggest that C. jejuni can induce IL-8 release from INT407 cells by t wo independent mechanisms, one of which requires adherence and/or invasion and the second of which requires CDT.