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Molecular mechanisms of regulation of abdominal adhesion formation by anti-IL-6 antibody.

Research Project

Project/Area Number 18H02885
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionHyogo Medical University

Principal Investigator

Fujimoto Jiro  兵庫医科大学, 医学部, 特別招聘教授 (90199373)

Co-Investigator(Kenkyū-buntansha) 石戸 聡  兵庫医科大学, 医学部, 教授 (10273781)
筒井 ひろ子  兵庫医科大学, 医学部, 教授 (40236914)
Qin XianYang  国立研究開発法人理化学研究所, 開拓研究本部, 研究員 (60756815)
宇山 直樹  兵庫医科大学, 医学部, 非常勤講師 (70402873)
波多野 悦朗  兵庫医科大学, 医学部, 非常勤講師 (80359801)
小嶋 聡一  国立研究開発法人理化学研究所, 生命医科学研究センター, ユニットリーダー (10202061)
宮下 正寛 (裴)  兵庫医科大学, 医学部, 講師 (30423883)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords術後癒着 / 線維化 / 腹膜中皮細胞 / IL-6 / TNF / TGF / トロンビン / 外科手術後癒着 / 腹膜内皮細胞 / 好中球 / 癒着 / 外科手術術後 / 免疫 / サイトカイン / 中皮細胞 / マイクロアレイ / 抗IL-6受容体抗体 / IL-6受容体 / 線維形成 / 抗体 / 外科手術 / 血液凝固
Outline of Final Research Achievements

We reported importance of neutrophil, IL-6, TNF, TGF in the progress of adhesion formation. (Scientific Reports: 2019: 9: 17558. Next we investigated he importance of anti-TNF medicine. We have used the monoclonal antibody of TNF which results
inhibition of abdominal adhesion in mice model. (Cell Physiol Biochem: 2020: 54: 1041-53), Moreover We investigated the role of anti thrombin and NETS, and found theta they also blocked the adhesion formation in mice. (Cell Physiol Biochem: 2021: 55: 400-412).

Academic Significance and Societal Importance of the Research Achievements

本研究によりこれまでは不明であった外科手術により生じる腹部癒着の分子機構が解明され、またその予防法も発見された。具体的には手術侵襲による腹膜中皮細胞の障害、それにより惹起されるIL-6、IFN-g、TNF、TGFの活性化により、腹膜中皮細胞自身myofibroblastに変身し、線維に置き換わる事実である。またこの研究の結果、IL-6のモノクロ抗体、TNFのモノクロ抗体、AT-III阻害剤により癒着が制御されることもマウスモデルで証明されこれらの薬剤は既に日常臨床で使用されており、近い将来、腹部癒着制御に関して臨床で使用される可能性を示した。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (7 results)

All 2021 2020 2019

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (3 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Antithrombin together with NETs inhibitor protected against postoperative adhesion formation in mice.2021

    • Author(s)
      m. Sudo, J xu, K. Mitani, M. Jimbo, H. Tsutsui, E. Hatano, J. Fujimoto
    • Journal Title

      Cell Physiol Biochem

      Volume: 55 Issue: 4 Pages: 400-412

    • DOI

      10.33594/000000392

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Blockede of tumor necrosis factor by etanercept prevents postoperative adhesion formation in mice.2020

    • Author(s)
      M. Sudo, K. Iida, H. Tsutsui, K. Mitani, M. Jimbo, E. Hatano, J. Fujimoto
    • Journal Title

      Cell Physiol Biochem

      Volume: 54 Pages: 1041-1053

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Effect of Daikenchuto, Japanese Herbal Medicine, on Adhesion Formation Induced by Cecum Cauterization and Cecum Abrasion in Mice2019

    • Author(s)
      Wu S, Uyama N, Itoh RA, Hatano E, Tsutsui H, Fujimoto J.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 2 Pages: 179-186

    • DOI

      10.1248/bpb.b18-00543

    • NAID

      130007590243

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-02-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-interleukin-6 receptor antibody treatment ameliorates postoperative adhesion formation2019

    • Author(s)
      Naoki Uyama, Hiroko Tsutsui, Songtao Wu, Koubun Yasuda, Etsuro Hatano, Xian-Yang Qin, Soichi Kojima, Jiro Fujimoto
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 17558-17571

    • DOI

      10.1038/s41598-019-54175-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Anti-IL-6 Receptor Monoclonal Antibody Robustly Ameliorated Postoperative Adhesion Formation in Mice.2019

    • Author(s)
      J Fujimoto, N. Uyama, H. Tsutsui, W, Songtao, M. Sudo, E. Hatano
    • Organizer
      15th Annual Academic Surgical Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Anti-IL-6 receptor monoclonal antibody robustry ameliorated p ostoperative adhesion formation in mice.2019

    • Author(s)
      Fujimoto J, Uyama N,Tsutsui H, Wu S.
    • Organizer
      The 14th Annual Academic Surgical Congress. Huston, 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] IL-6 may regulate adhesion formation induced by cecum cauterization in mice.2019

    • Author(s)
      Uyama N, Fujimoto J, Tsutsui H, Wu S.
    • Organizer
      The 14th Annual Academic Surgical Congress. Huston, 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-01-30  

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