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Interstitial lung inflammation with alveolar hemorrhage in mice

Research Project

Project/Area Number 18K07806
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionSaitama Children's Medical Center

Principal Investigator

Sato Satoshi  埼玉県立小児医療センター (臨床研究部), 感染免疫科, 医長 (60385028)

Co-Investigator(Kenkyū-buntansha) 菅沼 栄介  埼玉県立小児医療センター (臨床研究部), 感染免疫科, 副部長 (60408010)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords皮膚筋炎 / 若年性皮膚筋炎 / 間質性肺炎 / MDA5 / 抗MDA5抗体 / 疾患モデル作成 / マクロファージ / サイトカイン
Outline of Final Research Achievements

Anti-MDA5 antibody is associated with interstitial lung disease (ILD) in patients with juvenile dermatomyositis (JDM). Methods: MRL/Mp-lpr/lpr mice. They received pristane IP. And recombinant human MDA5 protein (rMDA5) was instilled. Results: H&E staining of lung from WT mouse compared with lung from a MRL/lpr mouse treated with pristane + rMDA5 protein showing mild thickening of the alveolar septa despite the alveolar hemorrhage. And perivascular lymphocytes infiltrate in a MRL/lpr mouse rather than a WT mouse treated with pristane + rMDA5 protein. The Lymphocyte infiltrations around alveolar macrophages was more prominent in MRL/lpr mouse treated with pristane + rMDA5 protein than other mouse.
Conclusions: These results suggest that lung involvements such as the alveolar hemorrhage, are caused by pristeine and rMDA5 prtotein in the pathogenesis of interstitial pneumonia.

Academic Significance and Societal Importance of the Research Achievements

本研究ではMDA5が肺組織において炎症を惹起、増悪させる因子働くことが推察された。炎症細胞の浸潤とともに肺組織の破壊が起こっている。一方で自己免疫応答の機序の検討は本研究では充分に行うことができていない。今後の課題と考える。
現在も抗MDA5抗体関連お皮膚筋炎、間質性肺炎の病態は解明されていないため本研究のデータをもとに更なる検討を行うことで病態の解明がさらに進み、治療に結びつく可能性がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (1 results)

All 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results)

  • [Journal Article] Clinical features of macrophage activation syndrome as the onset manifestation of juvenile systemic lupus erythematosus.2019

    • Author(s)
      45.Sato S, Uejima Y, Arakawa Y, Furuichi M, Suganuma E, Fujinaga S, Nakazawa A, Kawano Y.
    • Journal Title

      Rheumatol Adv Pract.

      Volume: 14 Issue: 1 Pages: 013-013

    • DOI

      10.1093/rap/rkz013

    • Related Report
      2019 Research-status Report
    • Peer Reviewed

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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