title: Early functional effects of Clostridium difficile toxin A on human colonocytes.
abstract: OBJECTIVE
  Previous in vitro studies have shown that Clostridium difficile toxin A is able to directly affect the intestinal epithelial barrier function. The aim of this study was to examine the early effects of toxin A on mucin exocytosis and determine whether this toxin can induce the production of the chemokine interleukin 8 (IL-8) from human colonic epithelial cells.
  
  
  METHODS
  Two model systems were used: the HT29-CI.16E colonic goblet cell line and primary cultures of human normal colonocytes.
  
  
  RESULTS
  Toxin A exerted a rapid and dose-related inhibition of stimulated mucin exocytosis without altering baseline (constitutive) mucin exocytosis from HT29-CI.16E cells. Toxin A was also able to induce the secretion of IL-8 from both HT29-CI.16E cells and primary cultures of human normal colonocytes, as early as 2-3 hours of incubation.
  
  
  CONCLUSIONS
  The results show that while toxin A is able to down-regulate stimulated mucin exocytosis, it is able to up-regulate the secretion of an important chemoattractant chemokine, IL-8. These modifications illustrate the ability of colonocytes to recruit inflammatory and immune cells that will eventually bring about major mucosal damage.
authors.affiliation: Groupe de Recherche Fonctions Secretoires des Epitheliums Digestifs, CJF INSERM 94-04, Faculte de Medecine, Nantes, France.
authors.forename: J E
authors.initials: JE
authors.lastname: Branka
authors.forename: G
authors.initials: G
authors.lastname: Vallette
authors.forename: A
authors.initials: A
authors.lastname: Jarry
authors.forename: C
authors.initials: C
authors.lastname: Bou-Hanna
authors.forename: P
authors.initials: P
authors.lastname: Lemarre
authors.forename: P N
authors.initials: PN
authors.lastname: Van
authors.forename: C L
authors.initials: CL
authors.lastname: Laboisse
mesh_terms: D001427:Bacterial Toxins; D002460:Cell Line; D003106:Colon / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000633:toxicity*; D006801:Humans; D013997:Time Factors
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile