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Analysis of the molecular mechanism by which extracellular acidification promotes LPA-induced inflammatory responses in rheumatoid arthritis synovial cells.

Research Project

Project/Area Number 15K08122
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionTokushima Bunri University

Principal Investigator

Nochi Hiromi  徳島文理大学, 薬学部, 教授 (30183552)

Co-Investigator(Kenkyū-buntansha) 伊藤 康一  徳島文理大学, 薬学部, 教授 (30291149)
Research Collaborator Tamoto Koichi  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords関節リウマチ / 滑膜細胞 / プロトン感知性受容体 / リゾホスファチジン酸 / リゾリン脂質 / マトリックスメタロプロテアーゼ / ADAMTS4 / COX-2
Outline of Final Research Achievements

In RA, the proliferation of synovial cells is abnormally augmented and the pH of synovial fluid from RA patients is lower than that from healthy individuals. Therefore, we hypothesized that local acidification in the intra-articular cavity affects inflammatory responses.
The results revealed that an acidic extracellular pH induced COX-2 and ADAMTS-4 expressions through G protein-coupled pH-sensing receptor OGR1 in RA synovial cells from RA patients. Furthermore, the acidic extracellular pH synergistically enhanced LPA-induced COX-2 and ADAMTS-4 expressions.The results suggest that the acidification of synovial fluid is involved in exacerbation of the RA pathology by amplifying the inflammatory mediator-induced inflammatory response.

Report

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

    (3 results)

All 2017 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (2 results)

  • [Journal Article] Levetiracetam treatment influences blood-brain barrier failure associated with angiogenesis and inflammatory responses in the acute phase of epileptogenesis in post-status epilepticus mice2016

    • Author(s)
      Kouichi Itoh, Yasuhiro Ishihara, Rie Komori, Hiromi Nochi, Ruri Taniguchi, Yoichi Chiba, Masaki Ueno, Fuyuko Takata-Tsuji, Shinya Dohgu, Yasufumi Kataoka
    • Journal Title

      Brain Research

      Volume: 1652 Pages: 1-13

    • DOI

      10.1016/j.brainres.2016.09.038

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 細胞外pHの酸性化は関節リウマチ滑膜細胞のADAMTS4発現を誘導する2017

    • Author(s)
      深田和寛、岡島史和、田元浩一、野地裕美
    • Organizer
      日本薬学会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2017-03-27
    • Related Report
      2016 Research-status Report
  • [Presentation] 食用油が変敗する条件の検討と変敗食用油が免疫系に与える影響の解析2017

    • Author(s)
      竹内 一、大岡嘉治、野地裕美
    • Organizer
      第13回日本食品免疫学会
    • Related Report
      2017 Annual Research Report

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

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