Early functional effects of Clostridium difficile toxin A on human colonocytes

JE Branka, G Vallette, A Jarry, C Bou-Hanna… - Gastroenterology, 1997 - Elsevier
JE Branka, G Vallette, A Jarry, C Bou-Hanna, P Lemarre, PN Van, CL Laboisse
Gastroenterology, 1997Elsevier
BACKGROUND & AIMS: 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 …
BACKGROUND & AIMS
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. (Gastroenterology 1997 Jun;112(6):1887-94)
Elsevier