Anti-inflammatory and anti-fibrotic effects of a novel macrophage-inhibitory protein in interstitial pneumonia

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08450
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Osaka Medical and Pharmaceutical University
• Principal Investigator: TAKEUCHI Tohru 大阪医科薬科大学, 医学部, 教授 (10330078)
• Co-Investigator(Kenkyū-buntansha): 鈴鹿 隆保 大阪医科薬科大学, 医学部, 助教 (50748225) ; 池本 正生 長浜バイオ大学, バイオサイエンス学部, 客員教授 (80144385) ; 小谷 卓矢 大阪医科薬科大学, 医学部, 特別職務担当教員(講師) (80411362) ; 岡田 光貴 京都橘大学, 健康科学部, 専任講師 (80747569)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 間質性肺疾患 / 膠原病 / S100タンパク質

Outline of Final Research Achievements

Activation of Macrophage is involved in the pathogenesis of interstitial pneumonia (IP) related to connective tissue diseases. This study demonstrated the effects of a recombinant protein (MIKO-I) targeting in S100A8/A9 protein in a bleomycin (BLM)-induced model (in vivo) and in murine peritoneal macrophages and human-derived cell lines (in vitro).
MIKO-I suppressed the lung inflammation and fibrosis by regulating inflammatory cytokines and S100 proteins in BLM-induced IP model. The agent also inhibited the polarization of macrophages to M2, which is associated with fibrosis, in murine peritoneal macrophages in vitro. Similar effects were shown in a human-derived cell line, THP-1.
This study presented that S100A8/A9 protein played a crucial role of in IP and MIKO-I is a potential agent for the treatment of IP.

Free Research Field

リウマチ学

Academic Significance and Societal Importance of the Research Achievements

MIKO-IはS100タンパク質A8/A9を標的としてマクロファージ活性化を抑制することでIPにおける肺組織での炎症と線維化を抑制する。この結果から、S100タンパク質A8/A9およびマクロファージがIPの病態に重要な役割を果たしていることを示しただけでなく、マクロファージ活性化が病態に大きく関わるIPを始めとする病態に対してMIKO-Iが新たな治療薬候補として考えられた。