Elucidation of the role of nitric oxide in the pathogensis and exacebation of chronic obstructive pulmonary disease and bronchial asthma using nitric oxide synthase deficient mice

• Project/Area Number: 15K09236
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: YATERA Kazuhiro 産業医科大学, 医学部, 教授 (40341515)
• Co-Investigator(Kenkyū-buntansha): 迎 寛 産業医科大学, 医学部, 非常勤医師 (80253821)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 一酸化窒素 / 一酸化窒素合成酵素 / 気管支喘息 / 慢性閉塞性疾患 / マクロファージ / 慢性閉塞性肺疾患 / マウス / 一酸化窒素合成酵素完全欠損マウス / COPD / 間質性肺炎

Outline of Final Research Achievements

We studied using nitric oxide synthase (NOS) completely deficient mice.
First, bronchial asthma mouse model was prepared using ovalbumin. As a result, eosinophilic inflammation, bronchial wall thickening, mucin production decreased in NOS completely deficient mice, and Th2 cytokines such as IL-4, IL-5 and IL-13 in the lung tissue decreased. Next, chronic obstructive pulmonary disease mouse model was prepared using pig pancreatic elastase. As a result, a significant increase of alveolar bulkhead distance and an increase of inflammatory cells were observed in NOS completely deficient mice. Thus, we suggest that NO is deeply involved in the pathology of bronchial asthma and chronic obstructive pulmonary disease.

Research Products

• [Journal Article] Protective Role of Myelocytic Nitric Oxide Synthases Against Hypoxic Pulmonary Hypertension in Mice. (2018)
  • Author(s): Ogoshi T, Tsutsui M, Kido T, Sakanashi M, Naito K, Oda K, Ishimoto H, Yamada S, Wang KY, Toyohira Y, Izumi H, Masuzaki H, Shimokawa H, Yanagihara N, Yatera K, Mukae H.
  • Journal Title: Am J Respir Crit Care Med. Volume: - Issue: 2 Pages: 232-244
  • DOI: 10.1164/rccm.201709-1783oc
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ｄｅｃｒｅａｓｅｄ ｂｒｏｎｃｈｉａｌ ｅｏｓｉｎｏｐｈｉｌｉｃ ｉｎｆｌａｍｍａｔｉｏｎ ａｎｄ ｍｕｃｏｓ ｈｙｐｅｒｓｅｃｒｅｔｉｏｎ ｉｎ ａｓｔｈｍａｔｉｃ ｍｉｃｅ ｌａｃｋｉｎｇ ａｌｌ ｎｉｔｒｉｃ ｏｘｉｄｅ ｓｙｎｔｈａｓｅ ｉｓｏｆｏｒｍｓ (2016)
  • Author(s): Ａｋａｔａ Ｋ， Ｙａｔｅｒａ Ｋ， Wang KY, Naito K, Ogoshi T, Noguchi S, Kido T, Toyohira Y, Shimokawa H, Yamagihara N, Tsutsui M, Mukae H
  • Journal Title: Ｌｕｎｇ Volume: 194 Issue: 1 Pages: 121-124
  • DOI: 10.1007/s00408-015-9833-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 低酸素性肺高血圧における骨髄NO合成酵素系の保護的役割 (2017)
  • Author(s): 生越貴明
  • Organizer: 第26回Pneumo Forum
• [Book] アレルギーの臨床 (2015)
  • Author(s): 矢寺和博
  • Publisher: ニューサイエンス社