title: Helicobacter pylori activates gastric epithelial cells to produce interleukin-8 via protease-activated receptor 2.
abstract: OBJECTIVE
  Recently, it has been shown that serine proteases derived from microorganisms stimulate epithelial cells to produce inflammatory mediators through protease-activated receptor (PAR). We investigated the involvement of PAR2 in the interleukin (IL)-8 production by Helicobacter pylori-infected gastric epithelial cells.
  
  
  RESULTS
  Human gastric epithelial cells, MKN45 cells, were used. The expression of PAR2 was assessed by real-time PCR and immunocytochemistry, and IL-8 protein was measured by an enzyme-linked immunosorbent assay. PAR2 mRNA and protein were constitutively expressed on unstimulated MKN45 cells. The treatment of cells with H. pylori resulted in a significant increase in PAR2 expression. In addition, trypsin (a natural PAR2 agonist), SLIGKV amide (a synthetic PAR2 agonist), H. pylori live bacteria or H. pylori culture supernatant significantly induced IL-8 production from MKN45 cells. H. pylori-induced IL-8 production was inhibited by nafamostat mesilate (a serine protease inhibitor), neutralizing antibody to PAR2 and in PAR2-deficient cells treated with siRNA.
  
  
  CONCLUSIONS
  These results reveal that H. pylori-derived protease activates gastric epithelial cells to produce inflammatory cytokines through PAR2, suggesting an important role for PAR2 in the modulation of gastric inflammation associated with H. pylori.
authors.affiliation: Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kajikawa
authors.forename: Norimasa
authors.initials: N
authors.lastname: Yoshida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katada
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Hirayama
authors.forename: Osamu
authors.initials: O
authors.lastname: Handa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D001550:Benzamidines; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology; D015870:Gene Expression; D006146:Guanidines / Q000494:pharmacology; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori / Q000201:enzymology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D044464:Receptor, PAR-2 / Q000819:agonists / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D014162:Transfection
chemical_list: D000906:Antibodies; D001550:Benzamidines; D006146:Guanidines; D016209:Interleukin-8; D034741:RNA, Small Interfering; D044464:Receptor, PAR-2; D015842:Serine Proteinase Inhibitors; C032855:nafamostat