Early Functional Effects of Clostridium difficile Toxin A on Human Colonocytes

Abstract : Background & Aims: Previous in vitro studies have able to secrete interleukin 8 (IL-8) under appropriate shown that Clostridium difficile toxin A is able to distimulation. 7-9 Because IL-8 plays a key role in neutrorectly affect the intestinal epithelial barrier function. phil recruitment to sites of inflammation, 10 this finding The aim of this study was to examine the early effects supports the concept that the epithelium plays a central of toxin A on mucin exocytosis and determine whether role in triggering the inflammatory reaction associated this toxin can induce the production of the chemokine with various pathogens, including Clostridium difficile interleukin 8 (IL-8) from human colonic epithelial cells. toxins. However, the issue of whether this mechanism Methods: Two model systems were used: the HT29could apply to normal colonocytes has remained unset-Cl.16E colonic goblet cell line and primary cultures of tled because of the inability to maintain such cells in human normal colonocytes. Results: Toxin A exerted a culture. rapid and dose-related inhibition of stimulated mucin C. difficile produces two exotoxins: toxin A and toxin exocytosis without altering baseline (constitutive) mu-B. Toxin A has biological effects evidenced by the fact cin exocytosis from HT29-Cl.16E cells. Toxin A was that it induces a severe inflammatory enteritis in intestialso able to induce the secretion of IL-8 from both nal loop models 11 and activates granulocytes. 12 In addi-HT29-Cl.16E cells and primary cultures of human normal colonocytes, as early as 2-3 hours of incubation.