PGE2 is a direct and robust mediator of anion/fluid secretion by human intestinal epithelial cells

Intestinal epithelial cells (IECs) play an indispensable role in maintaining body fluid balance partly through their ability to regulate anion/fluid secretion. Yet in various inflammatory gastrointestinal diseases, over-secretion of anions results in symptoms such as severe diarrhoea. Endogenous mediators, such as vasoactive intestinal peptide or prostaglandin E-2 (PGE(2)), regulate intestinal anion/fluid secretion, but their direct effect on purified human IECs has never been described in detail. Based on a previously described intestinal organoid swelling model, we established a 3D-scanner-assisted quantification method to evaluate the anion/fluid secretory response of cultured human IECs. Among various endogenous secretagogues, we found that PGE(2) had the lowest EC50 value with regard to the induction of swelling of the jejunal and colonic organoids. This PGE(2)-mediated swelling response was dependent on environmental Cl- concentrations as well as on several channels and transporters as shown by a series of chemical inhibitor studies. The concomitant presence of various inflammatory cytokines with PGE(2) failed to modulate the PGE(2)-mediated organoid swelling response. Therefore, the present study features PGE(2) as a direct and robust mediator of anion/fluid secretion by IECs in the human intestine.