Bacteroides fragilis enterotoxin induces the expression of IL-8 and transforming growth factor-beta (TGF-beta) by human colonic epithelial cells

Bacteroides fragilis toxin (BFT) has been shown to be capable of inducing i ntestinal mucosal inflammation in animals. Such inflammation may be respons ible for diarrhoea, which occurs in some, but not all human carriers of ent erotoxigenic strains of B. fragilis (ETBF). We have studied responses to BF T by different human intestinal epithelial cell lines and subsequently inve stigated the expression of IL-8 and TGF-beta by T84 cells. The latter were selected because their responses to BFT, characterized by morphological cha nges and cell death by apoptosis, were similar to those we have recently ob served in primary human colonocytes. We show that BFT dose-dependently incr eased the expression of transcripts and protein of the polymorphonuclear ce ll chemoattractant IL-8. BFT also dose-dependently induced the release of T GF-beta, which has been shown to enhance the repair of the injured intestin al epithelium. However, the secreted TGF-beta was almost exclusively in the biologically inactive form, as determined by Mv1Lu bioassay. Our studies t herefore suggest that exposure of colonic epithelial cells in vivo to high concentrations of BFT can initiate an inflammatory response via secreted IL -8. BFT-induced release of latent TGF-beta may facilitate the subsequent re pair of the injured epithelium, following its activation by proteases from neighbouring cells. Variation in cytokine responses by colonic epithelial c ells in vivo could be an important determinant in the development of mucosa l disease and symptoms in response to ETBF.