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The involvement of proton-sensing receptor OGR1 in chronic airway inflammation and secretion.

Research Project

Project/Area Number 15K09213
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionUniversity of Fukui

Principal Investigator

ISHIZUKA TAMOTSU  福井大学, 学術研究院医学系部門, 教授 (50302477)

Co-Investigator(Renkei-kenkyūsha) OKAJIMA Fumikazu  青森大学, 薬学部, 教授 (30142748)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsプロトン / OGR1 / 気道炎症 / IL-8 / 気管支平滑筋細胞 / グルココルチコイド / ヒト気管支平滑筋細胞 / NF-kB / AP-1 / ステロイド / NF-kB / AP-1 / IL-8 / 遺伝子転写 / デキサメタゾン
Outline of Final Research Achievements

Human bronchial smooth muscle cells (BSMCs) are involved in airway inflammatio mation. Ovarian cancer G protein-coupled receptor 1 (OGR1) sense extracellular protons and mediate cytokine production in BSMCs. BSMCs were stimulated by pH 6.3 or pH 7.4-adjusted DMEM containing 0.1% BSA (0.1% BSA-DMEM). As a control stimulant, TNF-alpha (10 ng/ml) was used. IL-8 mRNA expression in BSMCs was quantified by RT-PCR. Acidic pH induced mRNA expression of IL-8 and a substantial amount of IL-8 production in BSMCs. BSMCs transfected by siRNA specific for OGR1 produced less IL-8 compared with those transfected non-targeting siRNA. PKC inhibitor, MEK 1/2 inhibitor, and the inhibitor of IkB phosphorylation reduced acidic pH-stimulated IL-8 production in BSMCs. Dexamethasone inhibited acidic pH-stimulated IL-8 production of BSMCs in a dose-dependent manner. Dexamethasone did not affect either phosphorylation or binding to consensus DNA site of NF-kB p65.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (15 results)

All 2018 2017 2016 2015

All Journal Article (5 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (8 results) Book (2 results)

  • [Journal Article] 気管支喘息の診断と治療2018

    • Author(s)
      石塚 全
    • Journal Title

      日本内科学会誌

      Volume: 107 Pages: 476-481

    • Related Report
      2017 Annual Research Report
  • [Journal Article] リポキシンとアレルギー2018

    • Author(s)
      石塚 全
    • Journal Title

      アレルギー・免疫

      Volume: 25 Pages: 372-381

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Association of C-Type Lectin Mincle with FcεRIβγ Subunits Leads to Functional Activation of RBL-2H3 Cells through Syk2017

    • Author(s)
      Honjoh Chisato、Chihara Kazuyasu、Yoshiki Hatsumi、Yamauchi Shota、Takeuchi Kenji、Kato Yuji、Hida Yukio、Ishizuka Tamotsu、Sada Kiyonao
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 46064-46064

    • DOI

      10.1038/srep46064

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nattokinase, profibrinolytic enzyme, effectively shrinks the nasal polyp tissue and decreases viscosity of mucus2017

    • Author(s)
      Takabayashi T, Imoto Y, Sakashita M, Kato Y, Tokunaga T, Yoshida K, Narita N, Ishizuka T, Fujieda S.
    • Journal Title

      Allergology International

      Volume: 66 Issue: 4 Pages: 594-602

    • DOI

      10.1016/j.alit.2017.03.007

    • NAID

      130006179497

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 気管支喘息患者のQOLに影響する因子2017

    • Author(s)
      石塚 全
    • Journal Title

      アレルギー・免疫

      Volume: 24 Pages: 1146-1154

    • Related Report
      2017 Annual Research Report
  • [Presentation] 細胞外pH低下によるヒト気管支平滑筋細胞のIL-8産生に対するステロイドの効果2017

    • Author(s)
      門脇麻衣子、三ツ井美穂、島田昭和、本定千知、梅田幸寛、森川美羽、安斎正樹、飴嶋慎吾、山田秀典、斎藤 悠、久田剛志、岡島史和、石塚 全
    • Organizer
      第57回日本呼吸器学会学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 細胞外pHの低下によるヒト気管支平滑筋細胞からのIL-8産生亢進の転写調節機序とステロイドの抑制効果2017

    • Author(s)
      門脇麻衣子、本定千知、梅田幸寛、森川美羽、安斎正樹、山田秀典、斎藤 悠、久田剛志、岡島史和、石塚 全
    • Organizer
      第66回日本アレルギー学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト気管支平滑筋細胞のプロトン感知性受容体OGR1を介するIL-8産生に対するステロイド薬の作用2016

    • Author(s)
      門脇麻衣子、石塚 全、ほか
    • Organizer
      第65回日本アレルギー学会学術大会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2016-06-17
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト気管支平滑筋細胞のプロトン感知性受容体OGR1を介するIL-8産生に対するステロイド薬の作用2016

    • Author(s)
      門脇麻衣子、石塚 全、ほか
    • Organizer
      第65回日本アレルギー学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2016-06-17
    • Related Report
      2015 Research-status Report
  • [Presentation] プロトン刺激によるヒト気管支平滑筋細胞のIL-8産生に対するステロイドの抑制効果2016

    • Author(s)
      門脇麻衣子、石塚 全、ほか
    • Organizer
      第56回日本呼吸器学会学術講演会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2016-04-08
    • Related Report
      2016 Research-status Report
  • [Presentation] プロトン刺激によるヒト気管支平滑筋細胞のIL-8産生に対するステロイドの抑制効果2016

    • Author(s)
      門脇麻衣子、石塚 全、ほか
    • Organizer
      第56回日本呼吸器学会学術講演会
    • Place of Presentation
      京都
    • Year and Date
      2016-04-08
    • Related Report
      2015 Research-status Report
  • [Presentation] 細胞外pH低下によるヒト気管支平滑筋細胞からのIL-8, アンフィレギュリン産生に関する検討2015

    • Author(s)
      門脇麻衣子、石塚 全、ほか
    • Organizer
      第64回日本アレルギー学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2015-05-26
    • Related Report
      2015 Research-status Report
  • [Presentation] プロトン刺激によりヒト気管支平滑筋細胞から誘導される因子の検討2015

    • Author(s)
      門脇麻衣子、石塚 全、ほか
    • Organizer
      第55回日本呼吸器学会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2015-04-17
    • Related Report
      2015 Research-status Report
  • [Book] 気管支サーモプラスティパーフェクトガイド2018

    • Author(s)
      森川美羽、石塚 全
    • Total Pages
      117
    • Publisher
      日本医事新報社
    • Related Report
      2017 Annual Research Report
  • [Book] 呼吸器疾患診断治療アプローチ 気管支喘息2017

    • Author(s)
      石塚 全
    • Total Pages
      384
    • Publisher
      中山書店
    • Related Report
      2017 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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