title: Production of prostaglandinE2 via bile acid is enhanced by trypsin and acid in normal human esophageal epithelial cells.
abstract: Several reports suggest that duodenogastroesophageal reflux may produce esophagitis, Barrett's esophagus and esophageal carcinoma. And it is well known that the incidence of adenocarcinoma arising from Barrett's esophagus has been increasing during the past decade. On the other hand, cyclooxygenase-2 and prostaglandins, produced by the catalytic reaction of cyclooxygenase-2, are considered to relate to carcinogenesis of the digestive tract and other malignant tumors. Recent reports suggest that cyclooxygenase-2 is induced in Barrett's esophagus and esophageal carcinoma. The purpose of this study is to investigate the reaction of cyclooxygenase-2 expression and prostaglandinE2 production on normal human esophageal epithelial cells cultured with gastroduodenal components. Normal human esophageal epithelial cells were cultured with chenodeoxycholic acid, trypsin and in acidic condition, individually and with different combinations of these three factors. After culturing, cyclooxygenase-2 expression in the cells and amount of prostglandinE2 in culture media was evaluated by immunoblotting and enzyme-immunoassay, respectively after culturing the cells. Cyclooxygenase-2 expression was up-regulated by bile acid and prostaglandinE2 production was enhanced by bile acid with trypsin, acidic condition or both of these components, without a synergistic effect on cyclooxygenase-2 expression. Production of prostaglandinE2 via these factors was suppressed by the cyclooxygenase-2 selective inhibitor JTE-522. The results suggest that duodenogastroesophageal reflux may induce cyclooxygenase-2 expression and prostaglandinE2 production in esophageal epithelial cells, cyclooxygenase-2 specific inhibitors may have a chemopreventive effect on esophageal carcinoma.
authors.affiliation: Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, 54-Syogoin Kawara-cho, Sakyoku, Kyoto 606-8507, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawabe
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimada
authors.forename: Toshiya
authors.initials: T
authors.lastname: Soma
authors.forename: Masato
authors.initials: M
authors.lastname: Maeda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Itami
authors.forename: Junichi
authors.initials: J
authors.lastname: Kaganoi
authors.forename: Tohru
authors.initials: T
authors.lastname: Kiyono
authors.forename: Masayuki
authors.initials: M
authors.lastname: Imamura
mesh_terms: D001557:Benzenesulfonates / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002635:Chenodeoxycholic Acid / Q000494:pharmacology*; D003470:Culture Media; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004383:Duodenogastric Reflux / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004947:Esophagus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008565:Membrane Proteins; D010080:Oxazoles / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D014357:Trypsin / Q000494:pharmacology*; D015854:Up-Regulation; D000096926:Benzenesulfonamides
chemical_list: D001557:Benzenesulfonates; D002635:Chenodeoxycholic Acid; D003470:Culture Media; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D007527:Isoenzymes; D008565:Membrane Proteins; D010080:Oxazoles; D011451:Prostaglandin-Endoperoxide Synthases; D014357:Trypsin; C110453:4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide; D000096926:Benzenesulfonamides; C496540:PTGS2 protein, human