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Challenges in the Development of Novel Inhalants Mediated by the Proton-Sensing Receptor OGR1 in Airway Inflammation

Research Project

Project/Area Number 18K08404
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionGunma University

Principal Investigator

Haruka Saito  群馬大学, 医学部附属病院, 助教 (80447268)

Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords気道炎症 / プロトン / 気管支喘息 / 炎症 / アレルギー
Outline of Final Research Achievements

It has been reported that the proton-sensing G protein-coupled receptor OGR1, which senses extracellular pH, acts as a sensor in environments with small pH changes. We used OGR1-deficient mice to analyze how OGR1 is involved in airway inflammation including asthma. OGR1 was also expressed in airway epithelial cells, airway smooth muscle cells, and other airway constituent cells, as well as CD4+ T cells obtained from parabronchial lymph nodes and splenocytes. In the hydrochloric acid-administered ARDS model, the total cell number, macrophages, and neutrophil numbers were significantly decreased in OGR1-deficient mice. Compared to the wild type, decreased IL-6 and TNF-α production in alveolar lavage fluid was observed. It was suggested that OGR1 acts to promote airway inflammation.

Academic Significance and Societal Importance of the Research Achievements

アトピー素因を持つ気管支喘息に対しては、現在生物学的製剤の開発により、劇的な治療の発展が認められているが、非アトピー性気管支喘息に対しての治療は未だ十分だと言えない。OGR1は気道構成細胞である気道上皮細胞、気管支平滑筋細胞に特異的に発現していることから、本研究のように気道上皮細胞に傷害を起こすHDM点鼻による気管支喘息モデルや塩酸投与によるARDSモデルの解析はOGR1の役割についてより詳細に解析できる可能性がある。さらに非アトピー性気管支喘息やARDSで産生が増加するIL-6をOGR1欠損マウスで抑制することがわかったため、OGR1は気道炎症の鍵を握っている可能性が示唆された。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (15 results)

All 2022 2021 2020 2019

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Design and Synthesis of Cyclopropane Congeners of Resolvin E3, an Endogenous Pro-Resolving Lipid Mediator, as Its Stable Equivalents.2022

    • Author(s)
      (2)Arai S, Fujiwara K, Kojima M, Aoki-Saito H, Yatomi M, Saito T, Koga Y, Fukuda H, Watanabe M, Matsunaga S, Hisada T, Shuto S
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 87(15) Issue: 15 Pages: 10501-10508

    • DOI

      10.1021/acs.joc.2c01110

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influence of obesity in interstitial lung disease associated with anti-aminoacyl-tRNA synthetase antibodies.2022

    • Author(s)
      Yamaguchi K, Fukushima Y, Yamaguchi A, Itai M, Shin Y, Uno S, Muto S, Kouno S, Tsurumaki H, Yatomi M, Aoki-Saito H, Hara K, Koga Y, Sunaga N, Endo Y, Motegi SI, Nakasatomi M, Sakairi T, Ikeuchi H, Hiromura K, Hisada T, Tsushima Y, Kuwana M, Maeno T.
    • Journal Title

      Respiratory Medicine

      Volume: Mar;193 Pages: 106741-106741

    • DOI

      10.1016/j.rmed.2022.106741

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Metal-Stimulated Interleukin-6 Production Through a Proton-Sensing Receptor, Ovarian Cancer G Protein-Coupled Receptor 1, in Human Bronchial Smooth Muscle Cells: A Response Inhibited by Dexamethasone2021

    • Author(s)
      Kadowaki Maiko、Sato Koichi、Kamio Hisashi、Kumagai Makoto、Sato Rikishi、Nyui Takafumi、Umeda Yukihiro、Waseda Yuko、Anzai Masaki、Aoki-Saito Haruka、Koga Yasuhiko、Hisada Takeshi、Tomura Hideaki、Okajima Fumikazu、Ishizuka Tamotsu
    • Journal Title

      Journal of Inflammation Research

      Volume: Volume 14 Pages: 7021-7034

    • DOI

      10.2147/jir.s326964

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of Resolvin E3, a Proresolving Lipid Mediator, and Its Deoxy Derivatives: Identification of 18-Deoxy-resolvin E3 as a Potent Anti-Inflammatory Agent2020

    • Author(s)
      Fukuda Hayato、Ikeda Hiroyuki、Muromoto Ryuta、Hirashima Koki、Ishimura Kohei、Fujiwara Koichi、Aoki-Saito Haruka、Hisada Takeshi、Watanabe Mizuki、Ishihara Jun、Matsuda Tadashi、Shuto Satoshi
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 85 Issue: 21 Pages: 14190-14200

    • DOI

      10.1021/acs.joc.0c01701

    • NAID

      120007168587

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Treatment with Tumor Necrosis Factor-α Inhibitors, History of Allergy, and Hypercalcemia Are Risk Factors of Immune Reconstitution Inflammatory Syndrome in HIV-Negative Pulmonary Tuberculosis Patients2019

    • Author(s)
      Hachisu Yoshimasa、Koga Yasuhiko、Kasama Shu、Kaira Kyoichi、Yatomi Masakiyo、Aoki-Saito Haruka、Tsurumaki Hiroaki、Kamide Yosuke、Sunaga Noriaki、Maeno Toshitaka、Ishizuka Tamotsu、Hisada Takeshi
    • Journal Title

      Journal of Clinical Medicine

      Volume: 9 Issue: 1 Pages: 96-96

    • DOI

      10.3390/jcm9010096

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Resolvin E3 attenuates allergic airway inflammation via the interleukin-23-interleukin-17A pathway2019

    • Author(s)
      Sato M, Aoki-Saito H, Fukuda H, Ikeda H, Koga Y, Yatomi M, Tsurumaki H, Maeno T, Saito T, Nakakura T, Mori T, Yanagawa M, Abe M, Sako Y, Dobashi K, Ishizuka T, Yamada M, Shuto S, Hisada T.
    • Journal Title

      FASEB J.

      Volume: 33 Issue: 11 Pages: 12750

    • DOI

      10.1096/fj.201900283r

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of Cyclic AMP Response Element Binding Activation in the ERK1/2 and p38 MAPK Signalling Pathway in Central Nervous System, Cardiovascular System, Osteoclast Differentiation and Mucin and Cytokine Production2019

    • Author(s)
      Koga Yasuhiko、Tsurumaki Hiroaki、Aoki-Saito Haruka、Sato Makiko、Yatomi Masakiyo、Takehara Kazutaka、Hisada Takeshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 6 Pages: 1346-1346

    • DOI

      10.3390/ijms20061346

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular acidification-induced CXCL8 production through a proton-sensing receptor OGR1 in human airway smooth muscle cells: a response inhibited by dexamethasone.2019

    • Author(s)
      M. Kadowaki, H. Yamada, K. Sato, H. Shigemi, Y. Umeda, M. Morikawa, Y. Waseda, M. Anzai, Y. Kamide, H. Aoki-Saito, T. Hisada, F. Okajima, T. Ishizuka
    • Journal Title

      J. Inflamm. (Lond.)

      Volume: 16 Issue: 1 Pages: 4-4

    • DOI

      10.1186/s12950-019-0207-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] プロトン感知性Gタンパク質共役型受容体OGR1の塩酸投与によるマウスARDSモデルにおける働き2022

    • Author(s)
      齋藤悠、茂木千尋、齋藤従道、鶴巻寛朗、矢冨正清、古賀康彦、佐藤真季子、山口彩、山口公一、砂長則明、前野敏孝、石塚全、岡島史和、久田剛志
    • Organizer
      第62回呼吸器学会学術講演会
    • Related Report
      2022 Research-status Report
  • [Presentation] マウスARDSモデルにおけるプロトン感知性Gタンパク質共役型受容体OGR1の働き2022

    • Author(s)
      齋藤悠、茂木千尋、齋藤従道、鶴巻寛朗、矢冨正清、古賀康彦、佐藤真季子、砂長則明、前野敏孝、石塚全、岡島史和、久田剛志
    • Organizer
      第71回アレルギー学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] ResolvinE3のアレルギー性気道炎症に対する作用機序の検討2020

    • Author(s)
      佐藤 真季子, 齋藤 悠, 古賀 康彦, 矢冨 正清, 鶴巻 寛朗, 前野 敏孝, 石塚 全, 土橋 邦生, 砂長 則明, 周東 智, 山田 正信, 久田 剛志
    • Organizer
      第60回日本呼吸器学会学術講演会
    • Related Report
      2020 Research-status Report
  • [Presentation] 樹状細胞に対する炎症収束性メディエーターResolvinE3の作用の検討2020

    • Author(s)
      佐藤 真季子, 齋藤 悠, 鶴巻 寛朗, 矢冨 正清, 古賀 康彦, 砂長 則明, 前野 敏孝, 石塚 全, 柳川 正隆, 佐甲 靖志, 阿部 充宏, 土橋 邦生, 周東 智, 久田 剛志
    • Organizer
      JSA/WAO joint congress 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Resolvin E1 and E3 dampens asthmatic inflammation in a murine model2020

    • Author(s)
      M. Sato, H. Aoki-Saito, H. Fukuda, Koga, M. Yatomi, H. Tsurumaki ,N.Sunaga, T.Maeno, K. Dobashi, M. Yamada, S. Shuto, T. Hisada,
    • Organizer
      European Respiratory Society 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 最近のアレルギーの知見~各科女性医師・若手医師の活躍というシンポジウムで、内科の立場から「Resolvin E3 (RvE3)のマウス気管支喘息モデルにおける効果に対する解析」2019

    • Author(s)
      齋藤 悠
    • Organizer
      第3回日本アレルギー学会関東地方会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Book] アレルギーの臨床2021

    • Author(s)
      齋藤(青木) 悠、齋藤従道、久田剛志
    • Total Pages
      3
    • Publisher
      北隆館/ニューサイエンス社
    • Related Report
      2020 Research-status Report

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Published: 2018-04-23   Modified: 2025-01-30  

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