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Role of purinergic signaling on macrophage function induced by stretch-mediated mechanical stimulation.

Research Project

Project/Area Number 20K16010
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionTakasaki University of Health and Welfare

Principal Investigator

ito masaaki  高崎健康福祉大学, 薬学部, 准教授 (30438759)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsマクロファージ / 機械的進展刺激 / プリン作動性シグナル / MCP-1 / P2Y6受容体 / 機械的刺激
Outline of Research at the Start

近年、国民病ともいえる糖尿病や動脈硬化の発症・進展の根底には、全身の軽度の炎症反応が重要であると認識されるようになってきた。炎症反応の中心的な役割を果たす免疫担当細胞にマクロファージがある。マクロファージは免疫担当細胞として気管支や肺胞、消化管などにも広く分布し、肺の伸展や腸の蠕動運動および外界の浸透圧変化によって機械的な刺激を常に受容しているが、その機能に対する影響は明らかにされていない。
本研究では、機械的刺激を介したマクロファージ機能制御のメカニズムについて検討し、今後益々増加するであろう虚血性脳・心疾患などの炎症を基盤とする疾患の病因解明ならびに新しい予防・治療法の開発を試みる。

Outline of Final Research Achievements

Macrophages, immune cells, are involved in a variety of inflammatory diseases. This study analyzed the effects of mechanical stretch stimulus on macrophage function. Mechanical stretch loading on macrophages resulted in the secretion of extracellular nucleotides such as adenosine triphosphate (ATP) and increased gene expression levels of chemokines such as monocyte chemoattractant protein-1 (MCP-1) in a P2Y6 receptor-dependent manner, which is one of the nucleotide receptors. In addition, the activation of protein kinases such as ERK and p38 was observed in the cells upon mechanical stress load. In particular, the activation of the ERK pathway was involved in the increased gene expression and protein production of MCP-1. These findings suggest that macrophages may be activated when they sense mechanical stress in the heart, lungs, or intestine, and may promote inflammatory responses and contribute to pathogenesis.

Academic Significance and Societal Importance of the Research Achievements

近年、我々の健康維持や疾患に物理的な力による調節が深く関わっていることが示唆されている。本研究では免疫担当細胞の一つであるマクロファージに焦点を当て心臓や肺、腸などの組織で受容する機械的な刺激の影響を検討した。マクロファージは、機械的刺激の負荷に応じて炎症性サイトカインや白血球遊走因子の発現を上昇させ炎症応答を促進する可能性が明らかとなった。本研究成果は、マクロファージがダイナミックな機械的刺激を受容する組織における病態、すなわち動脈硬化や肺や腸の炎症、心筋梗塞などのような病態の理解と新たな治療戦略の提示につながると期待される。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (44 results)

All 2024 2023 2022 2021 2020

All Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Open Access: 7 results) Presentation (30 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Enhancement of mast cells activation by ATP via P2X4 receptor2024

    • Author(s)
      Kazuki Yoshida , Masa-Aki Ito, Isao Matsuoka
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 159 Issue: 1 Pages: 39-43

    • DOI

      10.1254/fpj.23083

    • ISSN
      0015-5691, 1347-8397
    • Year and Date
      2024-01-01
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modulation of prostaglandin transport activity of SLCO2A1 by annexin A2 and S100A102024

    • Author(s)
      Nakamura Yoshinobu、Ito Masa-aki、Hoshino Yukino、Matsuoka Isao、Okada Toshiaki、Okada Yasunobu、Nakanishi Takeo
    • Journal Title

      American Journal of Physiology-Cell Physiology

      Volume: 326 Issue: 4 Pages: C1042-C1053

    • DOI

      10.1152/ajpcell.00701.2023

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amplification of poly(I:C)-induced interleukin-6 production in human bronchial epithelial cells by priming with interferon-γ2023

    • Author(s)
      Okuma Norikazu、Ito Masa-aki、Shimizu Tomoyoshi、Hasegawa Atsuya、Ohmori Shin’ya、Yoshida Kazuki、Matsuoka Isao
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 21067-21067

    • DOI

      10.1038/s41598-023-48422-9

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential Effects of Gq Protein-Coupled Uridine Receptor Stimulation on IL-8 Production in 1321N1 Human Astrocytoma Cells2022

    • Author(s)
      Ito Masa-aki、Kojima Erika、Yanagihara Yu、Yoshida Kazuki、Matsuoka Isao
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 45 Issue: 6 Pages: 691-697

    • DOI

      10.1248/bpb.b21-01020

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2022-06-01
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] P-Glycoprotein?Mediated Pharmacokinetic Interactions Increase Pimozide hERG Channel Inhibition2022

    • Author(s)
      Morishita Hiroki、Perera Liyanage Manosika Buddhini、Zhang Xieyi、Mizoi Kenta、Ito Masa-aki、Yano Kentaro、Ogihara Takuo
    • Journal Title

      Journal of Pharmaceutical Sciences

      Volume: 111 Issue: 12 Pages: 3411-3416

    • DOI

      10.1016/j.xphs.2022.09.025

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Exploratory study of oxatomide derivatives with high P2X7 receptor inhibitory activity2022

    • Author(s)
      Yamagiwa Noriyuki、Komine Mika、Hanaoka Fumi、Nobuta Tomoya、Yoshida Kazuki、Ito Masaaki、Matsuoka Isao
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 77 Pages: 129035-129035

    • DOI

      10.1016/j.bmcl.2022.129035

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] P2X4 receptor stimulation enhances MrgprB2-mediated mast cell activation and pseudoallergic reactions in mice2022

    • Author(s)
      Yoshida Kazuki、Tanihara Shota、Miyashita Yuki、Obayashi Kosuke、Ito Masa-aki、Yamamoto Kimiko、Imai Toshiyashu、Matsuoka Isao
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 18613-18613

    • DOI

      10.1038/s41598-022-21667-6

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synergistic Cytokine Production by ATP and PGE2 via P2X4 and EP3 Receptors in Mouse Bone-Marrow-Derived Mast Cells2022

    • Author(s)
      Obayashi Kosuke、Yoshida Kazuki、Ito Masa-aki、Mori Tetsuya、Yamamoto Kimiko、Imai Toshiyashu、Matsuoka Isao
    • Journal Title

      Cells

      Volume: 11 Issue: 4 Pages: 616-616

    • DOI

      10.3390/cells11040616

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] G蛋白質共役型受容体を介するホスホリパーゼCシグナル伝達系の調節機構2021

    • Author(s)
      伊藤政明, 松岡功
    • Journal Title

      脳神経内科

      Volume: 94 Pages: 507-514

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] マスト細胞のP2X4受容体活性化を介したアレルギー反応の増強.2021

    • Author(s)
      松岡功, 吉田一貴、伊藤政明
    • Journal Title

      アレルギーの臨床

      Volume: 41 Pages: 171-175

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] ATP/P2X4受容体枢軸によるIgE 依存性マスト細胞脱顆粒の増強反応2021

    • Author(s)
      松岡功, 吉田一貴、伊藤政明
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 75 Pages: 369-376

    • NAID

      40022504137

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Extracellular ATP Augments Antigen-Induced Murine Mast Cell Degranulation and Allergic Responses via P2X4 Receptor Activation2020

    • Author(s)
      Yoshida Kazuki、Ito Masa-aki、Sato Naoko、Obayashi Kosuke、Yamamoto Kimiko、Koizumi Schuichi、Tanaka Satoshi、Furuta Kazuyuki、Matsuoka Isao
    • Journal Title

      The Journal of Immunology

      Volume: 204 Issue: 12 Pages: 3077-3085

    • DOI

      10.4049/jimmunol.1900954

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gastrointestinal absorption of pimozide is enhanced by inhibition of P-glycoprotein2020

    • Author(s)
      Morishita Hiroki、Okawa Kozue、Ishii Misaki、Mizoi Kenta、Ito Masa-aki、Arakawa Hiroshi、Yano Kentaro、Ogihara Takuo
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 10 Pages: e0232438-e0232438

    • DOI

      10.1371/journal.pone.0232438

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒト培養気管支上皮細胞のpoly(I:C)誘発IL-6産生におけるIFN-γのプライミング効果2024

    • Author(s)
      伊藤 政明、大熊 範和、清水 千義、長谷川 敦也、大森 慎也、吉田 一貴、松岡 功
    • Organizer
      日本薬学会第144年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] マウスの大腸上皮細胞の遺伝子発現に対するP2X4受容体欠損の影響2024

    • Author(s)
      吉田 一貴、青木 亮、萩原 武蔵、伊藤 政明、松岡 功
    • Organizer
      日本薬学会第144年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Annexin A2およびS100A10がSLCO2A1のプロスタグランジンE2輸送活性に及ぼす影響2024

    • Author(s)
      中村 吉伸、伊藤 政明、星野 雪乃、松岡 功、岡田 俊昭、岡田 泰伸、中西 猛夫
    • Organizer
      日本薬学会第144年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Effects of novel P2Y6 receptor inhibitor on LPS-induced acute lung injury model in mice2023

    • Author(s)
      Masa-aki Ito,Tomoyoshi Shimizu, Atsuya Hasegawa, Norikazu Okuma, Kazuki Yoshida, Tomoko Mineno, Isao Matsuoka
    • Organizer
      日本薬理学会97年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Altered gene expression in colon in P2X4 receptor deficient mice2023

    • Author(s)
      Kazuki Yoshida,Ryo Aoki,Natsuki Asahina,Yoshiki Morihashi,Masa-aki Ito,Isao Matsuoka
    • Organizer
      日本薬理学会97年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Priming effects of IFN-γ on poly(I:C)induced IL 6 production in human bronchial epithelial cells.2023

    • Author(s)
      Norikazu Okuma, Masa-aki Ito, Tomoyoshi Shimizu, Atsuya Hasegawa, Shin’ya Omori, Kazuki Yoshida, Isao Matsuoka
    • Organizer
      日本薬理学会97年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] P-gp-mediated drug-drug interaction promotes gastrointestinal absorption of pimozide and the risk of QT prolongation due to hERG channel inhibition-Fundamental studies and validation in clinical practice.2023

    • Author(s)
      Liyanage Manosika Buddhini Perera, Hiroki Morishita, Masa-aki Ito, Hiroki Sunakawa, Takuo Ogihara.
    • Organizer
      日本医療薬学会第33年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Do hypotonicity and accessory proteins required for Maxi-Cl channel affect SLCO2A1-mediated prostaglandin E2 transport activity?2023

    • Author(s)
      Yoshinobu Nakamura, Masa-aki Ito, Yukino Hoshino, Isao Matsuoka, Takeo Nakanishi,
    • Organizer
      日本薬物動態学会第38年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 機械的進展刺激によるマクロファージ活性化における細胞外ヌクレオチドの影響2023

    • Author(s)
      伊藤 政明、長谷川 敦也、大熊 範和、吉田 一貴、松岡 功
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Research-status Report
  • [Presentation] マウス骨髄由来マスト細胞におけるインターロイキン6産生に及ぼすGi共役型受容体であるプロスタノイドEP3とアデノシンA3受容体の作用の違い2023

    • Author(s)
      大林昂右、朝比奈愛理、伊藤政明、吉田一貴、松岡 功
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Research-status Report
  • [Presentation] ヒト気道上皮NCl-H292細胞のにおけるインターフェロン-γとPoly(I:C)共刺激で誘導される相乗的なIL-6産生機序の解析2023

    • Author(s)
      大熊範和,伊藤 政明,吉田 一貴,松岡 功
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Research-status Report
  • [Presentation] LPS誘発急性肺障害モデルマウスにおける新規P2Y6受容体阻害剤の薬効解析2023

    • Author(s)
      清水千義、伊藤政明 、峯野知子 、吉田一貴 、松岡功
    • Organizer
      147回日本薬理学会関東部会
    • Related Report
      2022 Research-status Report
  • [Presentation] マクロファージの機能に対する機械的伸展刺激の影響2023

    • Author(s)
      長谷川 敦也,伊藤 政明,吉田 一貴,松岡 功
    • Organizer
      147回日本薬理学会関東部会
    • Related Report
      2022 Research-status Report
  • [Presentation] Effects of extracellular nucleotides on macrophage activation induced by stretch-mediated mechanical stimulation.2022

    • Author(s)
      Masa-aki Ito,Atsuya Hasegawa,Norikazu Okuma,Kazuki Yoshida,Isao Matsuoka
    • Organizer
      日本薬理学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Effects of stretch-induced mechanical stimulation on macrophage function.2022

    • Author(s)
      Masa-aki Ito,Kazuki Yoshida,Isao Matsuoka
    • Organizer
      日本薬理学会
    • Related Report
      2021 Research-status Report
  • [Presentation] P2X4 receptor signaling potentiate Mas-relate G protein-coupled receptor B2-induced mast cell degranulation2022

    • Author(s)
      Kazuki Yoshida,Kousuke Obayashi,Syouta Tanihara,Yuuki Miyashita,Masa-aki Ito,Isao Matsuoka,
    • Organizer
      日本薬理学会
    • Related Report
      2021 Research-status Report
  • [Presentation] P2X4受容体は偽アレルギー反応を増強する2022

    • Author(s)
      吉田一貴,谷原祥太, 宮下友希, 大林晃右, 伊藤政明, 松岡功
    • Organizer
      日本薬学会
    • Related Report
      2021 Research-status Report
  • [Presentation] ヒト気道上皮NCl-H292細胞のサイトカイン産生における IFN-γとPoly(I:C)の相乗効果2022

    • Author(s)
      大熊範和, 伊藤政明, 吉田一貴, 松岡功
    • Organizer
      日本薬学会
    • Related Report
      2021 Research-status Report
  • [Presentation] マスト細胞におけるATPとPGE2の共刺激による相乗的サイトカイン産生2022

    • Author(s)
      大林昂右,吉田一貴,伊藤政明,松岡功
    • Organizer
      日本薬学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 炎症病態モデルマウスにおける腸間膜動脈の血管機能解2022

    • Author(s)
      秋吉玲未乃,伊藤政明,吉田一貴,松岡功
    • Organizer
      日本薬学会
    • Related Report
      2021 Research-status Report
  • [Presentation] ヒト神経膠芽腫A172細胞におけるATPによるインターロイキン6産生亢進作用の解析2022

    • Author(s)
      青木楓佳, 伊藤政明, 吉田一貴, 松岡功
    • Organizer
      日本薬学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 低張性刺激がSLCO2A1のプロスタグランジンE2輸送能に及ぼす影響2022

    • Author(s)
      中村吉伸, 伊藤政明, 岡田俊昭, 岡田泰伸, 松岡功, 中西猛夫
    • Organizer
      日本薬学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Effects of hypotonic stress on prostaglandin E2 transport and Maxi-Cl channel activities of SLCO2A12022

    • Author(s)
      Yoshinobu Nakamura, Masa-aki Ito, Toshiaki Okada, Yasunobu Okada, Isao Matsuoka, Takeo Nakanishi
    • Organizer
      日本生理学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Effect of pimozide accumulation by P-glycoprotein (P-gp) inhibition on hERG channel on cardiomyocytes2022

    • Author(s)
      高橋佳佑, 石井美咲, 森下宙輝, 伊藤政明, 張協義, 上岡宏規, 溝井健太, 矢野健太郎, 荻原琢男
    • Organizer
      日本薬剤学会
    • Related Report
      2021 Research-status Report
  • [Presentation] The effect of P-gp mediated pharmacokinetic interactions on pimozide hERG channel inhibition2021

    • Author(s)
      Hiroki Morishita, Keisuke Takahashi, Misaki Ishii, Masa-aki Ito, Xieyi Zhang, Kenta Mizoi, Kentaro Yano, Takuo Ogihara
    • Organizer
      日本薬物動態学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Regulation by purinergic signal of glucose-induced insulin secretion from iGL insulinoma cells.2021

    • Author(s)
      Masa-aki Ito,Chinatsu Machida,Kazuki Yoshida,Isao Matsuoka
    • Organizer
      日本薬理学会
    • Related Report
      2020 Research-status Report
  • [Presentation] IL-33 affects the expression of purinergic receptors in bone marrow-derived mast cells.2021

    • Author(s)
      Kazuki Yoshida,Yuu Ishida,Masaaki Ito,Isao Matsuoka
    • Organizer
      日本薬理学会
    • Related Report
      2020 Research-status Report
  • [Presentation] マウス胸部大動脈器官培養による生理活性物質の血管機能に及ぼす影響の解析2021

    • Author(s)
      伊藤政明,中山睦子,吉田一貴,松岡功
    • Organizer
      日本薬学会
    • Related Report
      2020 Research-status Report
  • [Presentation] P2X4受容体が結合組織型マスト細胞の脱顆粒反応に及ぼす影響2021

    • Author(s)
      吉田一貴,伊藤政明,松岡功
    • Organizer
      日本薬学会
    • Related Report
      2020 Research-status Report
  • [Presentation] マスト細胞のサイトカイン産出に及ぼす細胞外ATPの作用2021

    • Author(s)
      大林昂右,吉田一貴,伊藤政明,松岡功
    • Organizer
      日本薬学会
    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] アレルギー反応に伴う症状の予防もしくは抑制または治療用の医薬品組成物2021

    • Inventor(s)
      吉田一貴,伊藤政明,松岡功
    • Industrial Property Rights Holder
      吉田一貴,伊藤政明,松岡功
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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