produces a thermostable direct haemolysin (TDH) that has been implicated in the pathogenesis of diarrhoeal disease caused by this organism. In previous work, TDH induced Cl secretion in human colonic epithelial cells that was dependent on the intracellular Ca concentration, [Ca]. This study investigated whether Cl secretion induced by TDH is influenced by the stage of maturation of intestinal epithelial cells. Two different human colonic cell lines, villus cell-like Caco-2 cells and crypt cell-like T84 cells, cultured by different methods to obtain differentiated samples, were used. When these cells were exposed to butyrate, a transcriptional regulator of differentiation genes, or co-cultured with 18Co cells, a human colonic fibroblast cell line, they showed increased trans-epithelial resistance and villus cell marker enzyme activity. In Caco-2 cells, exposure to butyrate or co-culturing with 18Co cells resulted in increased TDH binding, higher short-circuit currents (Isc) and greater [Ca]. These results suggest that sensitivity to TDH is affected by the stage of cellular differentiation of cultured intestinal epithelial cells.


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