title: Revaprazan, a novel acid pump antagonist, exerts anti-inflammatory action against Helicobacter pylori-induced COX-2 expression by inactivating Akt signaling.
abstract: Chronic gastric inflammation developing after Helicobacter pylori (H. pylori) infection is responsible for either dyspeptic symptom relevant to gastritis/peptic ulcer or gastric tumorigenesis, in which acid suppressants, especially proton pump inhibitors (PPIs), play role in relieving dyspepsia as well as the eradication regimen. Among several mediators engaged in propagating gastric inflammation after H. pylori infection, cyclooxygenase-2 (COX-2) might be the principal one, and several prescriptions have been made for decreasing the COX-2 levels. Multiple line of evidence are available for anti-inflammatory action of PPIs beyond acid suppression, but revaprazan, a novel acid pump antagonist launched in clinic, has also been suggested to exert significant anti-inflammatory actions as much as PPI. In the current study, we hypothesized that revaprazan could regulate H. pylori-driven COX-2 expression as one of its anti-inflammatory pharmacological actions. The changes of gastric COX-2 expression as well as responsible transcription factors were measured after H. pylori infection in the presence or absence of revaprazan. Infection of AGS cells with H. pylori induced significant up-regulation of COX-2 in time- and concentration-dependent manners, which was mediated by Akt phosphorylation. Revaprazan treatment significantly inhibited IkappaB-alpha degradation as well as Akt inactivation, resulting in attenuation of H. pylori-induced COX-2 expression. Additional rescuing action of revaprazan against H. pylori-induced cytotoxicity was noted. In conclusion, revaprazan imposed significant anti-inflammatory actions on H. pylori infection beyond acid suppression.
authors.affiliation: Laboratory of Translational Medicine Gachon University Lee Gil Ya Cancer and Diabetes Institute, Incheon 406-840, Korea.
authors.forename: Jeong-Sang
authors.initials: JS
authors.lastname: Lee
authors.forename: Ji-Yoon
authors.initials: JY
authors.lastname: Cho
authors.forename: Heup
authors.initials: H
authors.lastname: Song
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Kim
authors.forename: Ki-Baik
authors.initials: KB
authors.lastname: Hahm