title: Toxigenic C. difficile induced inflammatory marker expression by human intestinal epithelial cells is asymmetrical.
abstract: Clostridium difficile infection of the intestinal epithelium and consequent pseudomembranous colitis is an important cause of morbidity and mortality. Pathogenesis has been ascribed exclusively to toxin production. Using in vitro models of human intestinal epithelial layers, we show that exposure to toxigenic C. difficile upregulates epithelial expression of IL-8 and ICAM-1, two molecules important in neutrophil chemoattraction and adhesion and subsequent inflammation. IL-8 production was also stimulated by toxin-containing supernatants. C difficile induced IL-8 release was inhibited by specific antiserum. Increased ICAM-1 expression only occurred after basolateral exposure to C. difficile while apical exposure had no effect on ICAM-1 expression. However, transepithelial electrical resistance was impaired by apical exposure to bacterial suspensions. We suggest that apical exposure to C. difficile induces changes in epithelial layer integrity which allows the bacteria and/or the toxin access to the basolateral compartment where pathogenic inflammatory mechanisms are activated.
authors.affiliation: Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University College Dublin, Belfield Campus, Dublin 4, Ireland.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Canny
authors.forename: Denise
authors.initials: D
authors.lastname: Drudy
authors.forename: Padraic
authors.initials: P
authors.lastname: Macmathuna
authors.forename: Cliona
authors.initials: C
authors.lastname: O'farrelly
authors.forename: Alan W
authors.initials: AW
authors.lastname: Baird
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D001426:Bacterial Proteins / Q000633:toxicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D015415:Biomarkers; D016360:Clostridioides difficile / Q000378:metabolism*; D004553:Electric Conductivity; D004768:Enterotoxins / Q000633:toxicity*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D007118:Immunoassay; D007249:Inflammation / Q000378:metabolism* / Q000382:microbiology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*
chemical_list: D019138:Antibodies, Blocking; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D015415:Biomarkers; D004768:Enterotoxins; D016209:Interleukin-8; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D018799:Intercellular Adhesion Molecule-1