Proinflammatory Cytokines Suppress the Expression Level of Protease-Activated Receptor-2 through the Induction of iNOS in Rat Colon

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概要

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• Protease-activated receptor (PAR)-2 plays important roles in intestinal inflammatory responses and also contributes to intestinal digestive motility. In the distal colon of a rat experimental colitis model, expression level of PAR-2 mRNA was decreased, and relaxation through PAR-2 activation was attenuated. This study shows the effects of proinflammatory cytokines on changes to PAR-2 in rat colonic smooth muscle using an organ culture method. Colonic inflammation was induced in rats by administering dextran sodium sulphate in drinking water. Organ culture of distal colonic smooth muscle layer of normal rat was performed for up to 3 days. In the experimental colitis rat, mRNA expression levels of proinflammatory cytokines such as IL-1β and TNF-α increased with inflammation. After the incubation with IL-1β and TNF-α for 3 days, trypsin (PAR-2 agonist)-induced relaxation was attenuated, simultaneous with suppression of PAR-2 mRNA expression. Conversely, in this preparation, mRNA expression levels of iNOS were significantly increased. When l-NMMA was added to the medium with IL-1β and TNF-α, changes to PAR-2 by these cytokine recovered. Moreover, when samples were cultured with NOC-18 (slow-releasing NO donor) for 3 days, relaxation induced by trypsin and expression of PAR-2 mRNA were attenuated. These results suggest that suppression of PAR-2 expression under inflammatory conditions is at least partially induced by NO produced in the colonic muscularis externa by proinflammatory cytokines.

• 社団法人　日本獣医学会の論文

著者

• SATO Koichi

  Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University

• HORIE Ai

  Laboratory of Veterinary Pharmacology, Faculty of Agriculture, Yamaguchi University

• NAGAI Kazuki

  Laboratory of Veterinary Pharmacology, Faculty of Agriculture, Yamaguchi University

• OHKURA Shinsuke

  Laboratory of Veterinary Pharmacology, Faculty of Agriculture, Yamaguchi University

• OHAMA Takashi

  Center for Cell Signaling and Department of Microbiology, University of Virginia School of Medicine

• KOMATSU Hiroyuki

  Laboratory of Veterinary Pharmacology, Faculty of Agriculture, Yamaguchi University

• Sato Koichi

  Laboratory Of Signal Transduction Institute For Molecular And Cellular Regulation Gunma University

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