Early functional effects of Clostridium difficile toxin A on human colonocytes.
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.
Branka
J E
JE
Groupe de Recherche Fonctions Secretoires des Epitheliums Digestifs, CJF INSERM 94-04, Faculte de Medecine, Nantes, France.
Vallette
G
G
Jarry
A
A
Bou-Hanna
C
C
Lemarre
P
P
Van
P N
PN
Laboisse
C L
CL
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
D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile