The elucidation of pathogenic mechanisms of asthma via airway epithelial cells

• Project/Area Number: 24591467
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Teikyo University (2014); Saga University (2012-2013)
• Principal Investigator: SUZUKI SHOICHI 帝京大学, 医療共通教育研究センター, 講師 (40253695)
• Co-Investigator(Kenkyū-buntansha): IZUHARA Kenji 佐賀大学, 医学部, 教授 (00270463)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 気管支喘息 / ペルオキシダーゼ / ヒポチオシアン酸 / ペンドリン / 気道上皮細胞 / 喘息 / ヒポチオシアン酸イオン

Outline of Final Research Achievements

In this study, we first examined effects of hypothiocyanite (OSCN-) on airway epithelial cells using in vitro OSCN- production system. Next we examine asthma pathogenesis of the individual knockout mice of three kinds of heme-peroxidases, LPO, MPO, EPO, which catalyze thiocyanate to produce OSCN-. Finally we checked effects of methimazole, an inhibitor of all heme-peroxidases on airway inflammation. Here we showed that OSCN- in low doses was sensed by protein kinase A followed by activation of NF-kB in the airway epithelial cells, whereas OSCN- in high doses induced necrotic cell death. One defect of the three kinds of heme-peroxidases showed no dramatic alleviation of asthma pathogenesis, however, inhibition of all the heme-peroxidases with methimazole improved airway inflammation. Our data strongly suggest that inhibition of heme-peroxidase is a novel therapeutic strategy for asthma.

Research Products

• [Remarks] 分子生命科学講座分子医化学分野ホームページ
  • URL: http://www.biomol.med.saga-u.ac.jp/medbiochem/research.html