RRC ID 43232
著者 Kajikawa H, Yoshida N, Katada K, Hirayama F, Handa O, Kokura S, Naito Y, Yoshikawa T.
タイトル Helicobacter pylori activates gastric epithelial cells to produce interleukin-8 via protease-activated receptor 2.
ジャーナル Digestion
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.
巻・号 76(3-4)
ページ 248-55
公開日 2007-1-1
DOI 10.1159/000113041
PII 000113041
PMID 18196899
MeSH Antibodies / pharmacology Benzamidines Cell Line, Tumor Epithelial Cells / metabolism* Epithelial Cells / microbiology Gastric Mucosa / metabolism* Gastric Mucosa / microbiology Gene Expression Guanidines / pharmacology Helicobacter Infections / metabolism* Helicobacter pylori / enzymology* Humans Interleukin-8 / metabolism* RNA, Small Interfering / pharmacology Receptor, PAR-2 / agonists Receptor, PAR-2 / genetics Receptor, PAR-2 / immunology Receptor, PAR-2 / metabolism* Serine Proteinase Inhibitors / pharmacology Transfection
IF 2.692
引用数 24
WOS 分野 GASTROENTEROLOGY & HEPATOLOGY
リソース情報
ヒト・動物細胞