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Clinical significance of S100 proteins in connective tissue diseases associated with interstitial pneumonia

Research Project

Project/Area Number 20K16564
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionOsaka Medical and Pharmaceutical University

Principal Investigator

Hiramatsu Yuri  大阪医科薬科大学, 医学部, 助教 (70850072)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywordsrheumatic disease / interstitial pneumonia / S100 protein / calprotectin / 間質性肺炎 / マクロファージ / S100タンパク質 / 膠原病
Outline of Research at the Start

間質性肺炎(IP)は膠原病(CTD)に予後を規定する重要な合併症で、難治例もあり新たな治療法が求められている。CTD-IPの発症や病態形成にはTh1細胞やマクロファージの活性化が関与していることが報告されている。研究協力者は独自の発想で作製したS100タンパク質(S100A8およびS100A9)を標的とするリコンビナントタンパク質Xがブレオマイシン誘導性肺線維症マウスを用いin vivoの系においてIPの発症を抑制することを明らかにしたが、ヒトIPにおけるS100タンパク質の役割について十分な知見がない。本研究では、ヒトIPにおけるS100タンパク質の臨床的意義と既存のバイオマーカーとの関連性を明らかにする。

Outline of Final Research Achievements

S100A8/A9 (calprotectin) is associated with the fibrosis and inflammation in lung. The aim of this study is to reveal the role of serum S100A8/A9 proteins in connective tissue diseases associated with interstitial pneumonia (CTD-IP). Serum levels of S100A8, S100A9, and calprotectin in patients with CTD were higher than those in controls. Calprotectin was increased in microscopic polyangiitis (MPA)-IP and rheumatoid arthritis (RA)-IP. S100A8 was elevated in MPA-IP, systemic sclerosis-IP, and RA-IP. S100A9 was increased in MPA-IP. There were no significant differences in S100A8/A9 proteins between MPA with and without IP and no correlation between serum levels of S100A8/A9 proteins and KL-6. However, there were differences in S100A8/A9 proteins between other CTD with and without IP. S100A8/A9 proteins may be related to the pathogenesis of CTD-IP. Further studies are needed to show the relation between S100A8/A9 proteins and CTD-IP.

Academic Significance and Societal Importance of the Research Achievements

膠原病に伴う間質性肺炎(CTD-IP)においてS100A8/A9タンパク質血中濃度が高値であり、疾患、特に顕微鏡的多発血管炎と関節リウマチおよびIPとの関連が示唆された。これまでにS100A8/A9タンパク質は肺の炎症のみならず線維化に関与することが報告されている。本研究の結果から、S100A8/A9タンパク質がCTD-IPのバイオマーカーのみならず新たな治療標的となる可能性が示唆された。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2023-01-30  

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