title: The effect of rebamipide on the expression of proinflammatory mediators and apoptosis in human neutrophils by Helicobacter pylori water-soluble surface proteins.
abstract: BACKGROUND
  Helicobacter pylori infection elicits persistent neutrophil infiltration in gastric mucosa. The expression of cyclooxygenase (COX)-2 and inhibition of apoptosis in the neutrophils could contribute to the pathogenesis of H. pylori infection. Rebamipide, a mucosal protective and ulcer-healing drug, has been known to inhibit neutrophil activation.
  
  
  OBJECTIVE
  To evaluate the effect of rebamipide on the neutrophils activated by H. pylori water-soluble proteins.
  
  
  METHODS
  After neutrophils were stimulated with H. pylori water extract (HPWE) or pre-treated with rebamipide, the expression of COX-2 mRNA and protein was assessed by quantitative RT-PCR and Western blotting, respectively. Prostaglandin (PG) E2 synthesis was determined by radioimmunoassay. Neutrophil apoptosis was evaluated by cytosolic oligonucleosome-bound DNA ELISA and caspase-3 activity was measured by the detection of p-nitroanilide after cleavage from labelled substrate.
  
  
  RESULTS
  Stimulation with HPWE up-regulated COX-2 expression and PGE2 secretion, and inhibited neutrophil apoptosis. Rebamipide suppressed PGE2 secretion from neutrophils dose-dependently. Rebamipide, however, did not affect neutrophil apoptosis and caspase-3 activity.
  
  
  CONCLUSIONS
  Rebamipide effectively suppressed PGE2 secretion from neutrophils activated by H. pylori water-soluble proteins. This is another possible mechanism of gastric mucosal protection by rebamipide.
authors.affiliation: Department of Internal Medicine, Liver Research Institute and Clinical Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: J S
authors.initials: JS
authors.lastname: Kim
authors.forename: J M
authors.initials: JM
authors.lastname: Kim
authors.forename: H C
authors.initials: HC
authors.lastname: Jung
authors.forename: I S
authors.initials: IS
authors.lastname: Song
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D015854:Up-Regulation
chemical_list: D000897:Anti-Ulcer Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D015363:Quinolones; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020929:Mitogen-Activated Protein Kinase Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D015232:Dinoprostone; C052785:rebamipide; D000409:Alanine