Effect of a retinoid X receptor partial agonist on airway inflammation, airway hyperresponsiveness, and emphysema.

2017 Fiscal Year Final Research Report

• Project/Area Number: 26461189
• 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: Okayama University
• Principal Investigator: KANEHIRO ARIHIKO 岡山大学, 医学部, 客員研究員 (20243503)
• Co-Investigator(Kenkyū-buntansha): 宮原 信明 岡山大学, 保健学研究科, 教授 (70335610)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 気管支喘息 / 肺気腫 / COPD / 好酸球性気道炎症 / 好中球性気道炎症 / レチノイドX受容体 / レチノイドX受容体パーシャルアゴニスト / 核内受容体

Outline of Final Research Achievements

Oral administration of a novel Retinoid X receptor (RXR) partial agonist (NEt-4IB) significantly suppressed airway hyperresponsiveness, inflammatory cell accumulation in the airways, and attenuated the levels of TNF-α in the lung, and IL-5, IL-13 and NO levels in bronchoalveolar lavage fluid, and goblet cells hyperplasia and NF-κB expression in lung tissue in a murine model of asthma. Furthermore, in a porcine pancreas elastase (PPE)- and cigarette smoke extract (CSE)-induced emphysema model, treatment with NEt-4IB significantly suppressed the emphysematous changes and neutrophilic airway inflammation, proteinase/anti-proteinase imbalance, and increased anti-oxidant activity. These data suggest that RXRs may play crucial roles in the mechanism of airway inflammation, airway hyperresponsiveness, and emphysematous change, and the novel RXR partial agonist NEt-4IB may be a promising candidate for the treatment of asthma and COPD.

Free Research Field

呼吸器・アレルギー内科学