Estrogen-induced alteration of chronic obstructive pulmonary disease regulated by SAA/LXA4 balance

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K08647
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Fukuoka University
• Principal Investigator: Koji Tominaga 福岡大学, 薬学部, 准教授 (10509623)
• Co-Investigator(Kenkyū-buntansha): 古賀 允久 福岡大学, 薬学部, 准教授 (60570801) ; 山内 淳史 福岡大学, 薬学部, 教授 (90341453)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: エストロゲン / COPD / LXA4

Outline of Final Research Achievements

This study focused on the association between estrogen variation with aging in chronic obstructive pulmonary disease (COPD), an inflammatory lung disease, and serum amyloid A (SAA) and lipoxan A4 (LXA4), which are notable markers of chronic inflammation.
Ovariectomy, a model of menopause, exacerbated the expansion of alveolar diameter in elastase (PPE)-induced COPD model mice. The involvement of SAA in this phenomenon On the other hand, LXA4 increased or decreased in the presence and absence of estrogen and time course, and the distribution of LXA4 receptors in the lung also changed with a delay. This study showed that there is a complex linkage between estrogen and LXA4 over a time course.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

COPDにおいて、女性更年期でのエストロゲン減少がCOPD増悪に関与しており、LXA4とその受容体を制御していることが明らかとなった。LXA4は、アラキドン酸から合成される脂質メディエータであり、喘息と関係の深いロイコトリエンとの関係が深い。本研究により女性のCOPDにおいてはLXA4をターゲットとする治療が有効である可能性が示された。