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Role of BLT1 signaling in innate immune cells in liver repair

Research Project

Project/Area Number 18K15760
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKitasato University

Principal Investigator

Kojo Ken  北里大学, 医学部, 助教 (20525414)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsBLT1 / 肝修復 / 免疫細胞 / 好中球 / ロイコトリエン / 肝 / 修復 / 脂質メディエーター / 肝障害 / 組織修復
Outline of Final Research Achievements

The aims of the present study were to examine the roles of leukotriene B4 receptor (BLT1) in innate immune cells in liver repair after acetaminophen (APAP)-induced liver injury. We examined the role of BLT1 by comparing the responses of BLT1 knockout (BLT1-/-) mice and wild type (WT) mice in liver repair following APAP hepatotoxicity. Deletion of neutrophils delayed liver repair in APAP-treated WT mice. BLT1 deficiency delayed liver repair, associated with reduction in apoptotic neutrophils and restorative macrophages. Transfer of BLT1 deficient neutrophils impaired liver repair. Efferocytosis of apoptotic neutrophils was suppressed BLT1-/- mice. The stimulation of resolvin E1 promoted differentiation of macrophages to a restorative type in a BLT1 signaling dependent manner. These results indicate that BLT1 facilitates liver repair via resolvin E1-mediated efferocytosis of apoptotic neutrophils by reparative macrophages.

Academic Significance and Societal Importance of the Research Achievements

本研究は好中球BLT1シグナルが急性炎症の進行にだけでなく、炎症収束や組織修復にも関与するという従来とは異なるBLT1シグナルの役割を解明するものである。炎症組織が修復する過程には浸潤好中球から発信されるメッセージをマクロファージが受容することが重要である。本研究は、BLT1シグナルがレゾルビンRvE1を介して好中球とマクロファージによる一連の肝修復過程を連結させる作用があることを明らかにした。生体反応カスケードを連動させるBLT1シグナル伝達作用の機序の一端がが解明されたことによって、今後、生理活性脂質による肝再生治療法の開発につながることが期待される。

Report

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

    (7 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (2 results)

  • [Journal Article] Thromboxane A(2) receptor signaling in endothelial cells attenuates monocrotaline-induced liver injury.2019

    • Author(s)
      Otaka F, Ito Y, Inoue T, Ohkubo H, Nishizawa N, Kojo K, Betto T, Yamane S, Narumiya S, Koizumi W, Majima M
    • Journal Title

      Toxicol Appl Pharmacol

      Volume: 381 Pages: 114733-114733

    • DOI

      10.1016/j.taap.2019.114733

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] WiNTRLINC1/ASCL2/c-Myc Axis Characteristics of Colon Cancer with Differentiated Histology at Young Onset and Essential for Cell Viability2019

    • Author(s)
      Yokota K, Tanaka Y, Harada H, Kaida T, Nakamoto S, Soeno T, Fujiyama Y, Yokota M, Kojo K, Miura H, Yamanashi T, Sato T, Nakamura T, Watanabe M, Yamashita K.
    • Journal Title

      Ann Surg Oncol

      Volume: 26 Issue: 13 Pages: 4826-4834

    • DOI

      10.1245/s10434-019-07780-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive Genetic Search to Clarify the Molecular Mechanism of Drug Resistance Identifies ASCL2-LEF1/TSPAN8 Axis in Colorectal Cancer2019

    • Author(s)
      Tanaka T, Kojima K, Yokota K, Tanaka Y, Ooizumi Y, Ishii S, Kojo K, et al.
    • Journal Title

      Ann Surg Oncol

      Volume: 印刷中 Issue: 5 Pages: 1401-1411

    • DOI

      10.1245/s10434-019-07172-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epigenetic Status of CDO1 Gene May Reflect Chemosensitivity in Colon Cancer with Postoperative Adjuvant Chemotherapy.2019

    • Author(s)
      Yokoi K, Harada H, Yokota K, Ishii S, Tanaka T, Nishizawa N, Kojo K, et al.
    • Journal Title

      Ann Surg Oncol

      Volume: 26 Issue: 2 Pages: 406-414

    • DOI

      10.1245/s10434-018-6865-z

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of microsomal prostaglandin E synthase-1 facilitates liver repair after hepatic injury in mice.2018

    • Author(s)
      Nishizawa N, Ito Y, Eshima K, Ohkubo H, Kojo K, Inoue T, Raouf J, Jakobsson PJ, Uematsu S, Akira S, Narumiya S, Watanabe M, Majima M.
    • Journal Title

      J Hepatol.

      Volume: S0168-8278(18) Issue: 1 Pages: 30126-30130

    • DOI

      10.1016/j.jhep.2018.02.009

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 樹状細胞のEP3シグナル伝達はマウスの虚血再灌流障害後の肝修復を促進する。2020

    • Author(s)
      中本 修司、伊藤 義也、後藤 卓也、西澤 伸恭、古城 憲、隈元 雄介、馬嶋 正隆
    • Organizer
      日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 術前化学放射線療法施行後に行った腹腔鏡手術の治療成績2019

    • Author(s)
      佐藤 武郎、中村 隆俊、山梨 高広、三浦 啓壽、古城 憲、島津 将、萩原 千恵、丸山 正裕、坂本 純一、渡邊 昌彦
    • Organizer
      第90回大腸癌研究会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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