| セッション情報 |
International Forum 1(Gastrointestinal tract) 3.Pathogenesis of NSAIDs-enteropathy
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| タイトル |
IF1-3-IV (Plenary presentation) Role of protease/PAR2 pathway in the pathogenesis of indomethacin-induced rats enteritis
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| 演者 |
Kazuhiko Uchiyama（Inflammation and ImmunologyKyoto Prefectural University of MedicineKyotoJapan^1） |
| 共同演者 |
Norimasa Yoshida（Molecular Gastroenterology and HepatologyKyoto Prefectural University of MedicineKyotoJapan^2）, Tetsuya Okayama（Inflammation and ImmunologyKyoto Prefectural University of MedicineKyotoJapan^1）, Takahiro Suzuki（Inflammation and ImmunologyKyoto Prefectural University of MedicineKyotoJapan^1）, Tomohisa Takagi（Inflammation and ImmunologyKyoto Prefectural University of MedicineKyotoJapan^1）, Hiroshi Ichikawa（Inflammation and ImmunologyKyoto Prefectural University of MedicineKyotoJapan^1）, Toshikazu Yoshikawa（Inflammation and ImmunologyKyoto Prefectural University of MedicineKyotoJapan^1） |
| 抄録 |
（Background and Aims］ NSAIDs－induced enteropathy is clinically very important but the pathologicalmechanisms have been still unclear． We have previously reported that mast cells are involved in thepathogenesis of indomethacine－induced enteropathy． Mast cell－derived tryptase and luminal trypsin havebeen shown to activate protease－activated receptor 2 （PAR2）which induces inflammatory cytokine se－cretion from intestinal epithelial cells． ln this studywe investigated the role of protease／PAR 2 in in－domethacin－induced intestinal injury．［Methodsl Male Wistar rats were given indomethacin subcutaneously and the intestinal mucosal damagewas estimated after 24 hours． The area （mm2） of macroscopic visible lesionsmyeloperoxidase （MPO） ac－tivity as an index of neutrophil accumulationand histopathological manifestation were evaluate d． Mastcell tryptase and PAR2 were assessed by the immunohistochemical staining and real－time RT－PCRre－spectively． ln additionusing nafamostat mesilate （NM）a serine protease inhibitor which inhibit tryptaseand trypsin activityor PAR2 antagonistthe effect of protease／PAR2 in indo血ethacin－induced intestinalinjury was evaluated．［Results］ Subcutaneous administration of indomethacin resulted in severe intestinal mucosal injury withthe increase in MPO activitiesand enhanced microscopic findings which revealed the multiple hemor－rhagic erosionsedema and remarkable infiltration of inflammatory cells． ln additionindomethacin in－duced increase in mast cell tryptase and PAR2 expression in intestinal mucosa． ln rats treated with NM orPAR2 antagonistindomethacin－induced intestinal inflammation was significantly reduced．（Conclusionsl These results suggest that protease／PAR2 is involved in the indomethacin－induced smallintestinal lesions in ratssuggesting that anti－protease therapy using NM has excellent potential to be－come a new therapeutic strategy for NSAIDs－induced enteritis． |
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