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- Title
Helicobacter pylori Activates Gastric Epithelial Cells to Produce Interleukin-8 via Protease-Activated Receptor 2.
- Authors
Kajikawa, Hirokazu; Yoshida, Norimasa; Katada, Kazuhiro; Hirayama, Fumihiro; Handa, Osamu; Kokura, Satoshi; Naito, Yuji; Yoshikawa, Toshikazu
- Abstract
Background/Aim: 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. Methods and 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. Copyright © 2008 S. Karger AG, Basel
- Subjects
SERINE proteinases; MICROORGANISMS; EPITHELIAL cells; INTERLEUKINS; HELICOBACTER pylori; IMMUNOCYTOCHEMISTRY
- Publication
Digestion, 2008, Vol 76, Issue 3/4, p248
- ISSN
0012-2823
- Publication type
Article
- DOI
10.1159/000113041