Implication of proteinase/proteinase-activated receptor in gastrointestinal inflammation

  • Yoshida Norimasa
    Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Japan Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan
  • Yoshikawa Toshikazu
    Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan

書誌事項

タイトル別名
  • Basic and Translational Research on Proteinase-Activated Receptors: Implication of Proteinase/Proteinase-Activated Receptor in Gastrointestinal Inflammation
公開日
2008
資源種別
journal article
DOI
  • 10.1254/jphs.08r31fm
公開者
公益社団法人 日本薬理学会

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説明

Recently, the role of serine proteinases in the pathogenesis of inflammation and autoimmune diseases via interaction with the proteinase-activated receptor (PAR) has attracted attention. Activation of PAR has a pro-inflammatory effect through the overproduction of inflammatory cytokines such as interleukin (IL)-6 and IL-8. PAR2 activation in human esophageal epithelial cells by trypsin induces NFκB– and AP-1–dependent IL-8 production in association with activation of p38 MAPK and ERK1/2, suggesting that esophageal inflammation may be induced by PAR2 activation via reflux of trypsin. It has been also proposed that Helicobacter pylori (H. pylori) induces PAR expression in the gastric epithelial cells and H. pylori–derived serine proteinase promotes IL-8 production via PAR in the epithelial cells. In addition, an increase of PAR-dependent IL-8 production has been observed in H. pylori–infected human gastric mucosa, suggesting an important role for PAR2 in the modulation of gastric inflammation associated with H. pylori. Recent studies have strongly indicated that tryptase and PAR are implicated in the pathogenesis of inflammatory bowel disease and experimental colitis. We demonstrated that anti-tryptase therapy may become a new therapeutic strategy in human ulcerative colitis. Thus, the role of PAR in the gastrointestinal tract has been gradually clarified, but further investigations are needed because the receptor has a variety of functions.<br>

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