PGE2is 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 E2(PGE2), 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 PGE2had the lowest EC50value with regard to the induction of swelling of the jejunal and colonic organoids. This PGE2-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 PGE2failed to modulate the PGE2-mediated organoid swelling response. Therefore, the present study features PGE2as a direct and robust mediator of anion/fluid secretion by IECs in the human intestine.
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Satoru
S
Fujii
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Kohei
K
Suzuki
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Ami
A
Kawamoto
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Fumiaki
F
Ishibashi
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Toru
T
Nakata
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Tatsuro
T
Murano
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.|Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, Germany.
Go
G
Ito
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.|Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Hiromichi
H
Shimizu
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Tomohiro
T
Mizutani
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Shigeru
S
Oshima
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Kiichiro
K
Tsuchiya
Department of Advanced Therapeutics in GI Diseases, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Tetsuya
T
Nakamura
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Akihiro
A
Araki
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Kazuo
K
Ohtsuka
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.|Center for Stem Cell and Regenerative Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Ryuichi
R
Okamoto
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Mamoru
M
Watanabe
D000838:Anions / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000473:pathology; D007583:Jejunum / Q000166:cytology / Q000187:drug effects*; D009940:Organoids / Q000166:cytology / Q000378:metabolism
D000838:Anions; D002712:Chlorides; D015232:Dinoprostone