Early functional effects of Clostridium difficile toxin A on human colonocytes

Gastroenterology. 1997 Jun;112(6):1887-94. doi: 10.1053/gast.1997.v112.pm9178681.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Toxins*
  • Cell Line
  • Colon / cytology
  • Colon / drug effects*
  • Dose-Response Relationship, Drug
  • Enterotoxins / toxicity*
  • Humans
  • Time Factors


  • Bacterial Toxins
  • Enterotoxins
  • tcdA protein, Clostridium difficile