title: Campylobacter jejuni cytolethal distending toxin mediates release of interleukin-8 from intestinal epithelial cells.
abstract: Live cells of Campylobacter jejuni and Campylobacter coli can induce release of interleukin-8 (IL-8) from INT407 cells. Additionally, membrane fractions 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 defective in any of the three membrane-associated protein subunits of cytolethal distending toxin (CDT) were unable to induce IL-8. The presence of the three cdt genes on a shuttle plasmid in trans restored both CDT activity and the ability to release IL-8 to membrane fractions. However, CDT mutations did not affect the ability of 81-176 to induce IL-8 during adherence to or invasion of INT407 cells. When C. jejuni cdt genes were transferred on a shuttle plasmid into a C. coli strain lacking CDT, membrane preparations became 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. Antibodies against recombinant forms of each of the three CDT subunit proteins neutralized both CDT activity and the activity responsible for IL-8 release. The data suggest that C. jejuni can induce IL-8 release from INT407 cells by two independent mechanisms, one of which requires adherence and/or invasion and the second of which requires CDT.
authors.affiliation: Enteric Diseases Department, Naval Medical Research Center, Silver Spring, Maryland 20910, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: Hickey
authors.forename: A L
authors.initials: AL
authors.lastname: McVeigh
authors.forename: D A
authors.initials: DA
authors.lastname: Scott
authors.forename: R E
authors.initials: RE
authors.lastname: Michielutti
authors.forename: A
authors.initials: A
authors.lastname: Bixby
authors.forename: S A
authors.initials: SA
authors.lastname: Carroll
authors.forename: A L
authors.initials: AL
authors.lastname: Bourgeois
authors.forename: P
authors.initials: P
authors.lastname: Guerry
mesh_terms: D001427:Bacterial Toxins / Q000235:genetics / Q000633:toxicity*; D016123:Campylobacter jejuni / Q000472:pathogenicity*; D002478:Cells, Cultured; D004926:Escherichia coli / Q000472:pathogenicity; D005816:Genetic Complementation Test; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001427:Bacterial Toxins; D016209:Interleukin-8; C067044:cytolethal distending toxin