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The molecular mechanism of effects of midazolam on dendritic cells and immune response

Research Project

Project/Area Number 25462434
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionOsaka University

Principal Investigator

Ohta Noriyuki  大阪大学, 医学部附属病院, 助教 (60379162)

Co-Investigator(Kenkyū-buntansha) FUJINO Yuji  大阪大学, 大学院医学系研究科(研究院), 教授 (50252672)
後藤 幸子  大阪大学, 医学(系)研究科(研究院), 助教 (20276710)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords樹状細胞 / Translocator protein / 免疫 / マクロファージ / TSPO / ベンゾジアゼピン / IL-6 / 一酸化窒素 / ミダゾラム / テトラマー / トランスジェニックマウス
Outline of Final Research Achievements

Benzodiazepine shows sedative effect that suppresses central nerve system via GABA receptor. On the other hand benzodiazepine has another functional molecule as translocator protein (TSPO). Benzodiazepine was reported that affects function of immune cells, but it is not uncertain about those of functional mechanism. We report that we found the mechanism of midazolam on immune cells. Using a murine macrophage cell line, RAW264 cells, we analyzed the effect of midazolam on the expression of CD80 and CD86 and the secretion of IL-6. Midazolam suppressed the expression of costimulatory molecules and IL-6. The activation of RAW264 was inhibited by TSPO ligand but not by GABA legends. Finally we analyzed the contribution of TSPO by analysis of using knockdown RAW264 cells by siRNA for TSPO. The effect of midazolam was inhibited by knockdown of TSPO. These results showed that midazolam has an inhibitory action of immune response on murine macrophages via TSPO.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (4 results)

All 2016 2014 2013

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (1 results) (of which Invited: 1 results)

  • [Journal Article] Haloperidol Suppresses NF-kappaB to Inhibit Lipopolysaccharide-Induced Pro-Inflammatory Response in RAW 264 Cells.2016

    • Author(s)
      Yamamoto S, Ohta N et al
    • Journal Title

      Med Sci Monit.

      Volume: 22 Pages: 367-372

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Haloperidol Suppresses Murine Dendritic Cell Maturation and Priming of the T Helper 1-Type Immune Response2014

    • Author(s)
      大田典之
    • Journal Title

      Anesth and analg

      Volume: 118

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The comparison of spontaneous breathing and muscle paralysis in two different severities of experimental lung injury.2013

    • Author(s)
      吉田健史
    • Journal Title

      Crit Care Med.

      Volume: 41 Issue: 2 Pages: 536-45

    • DOI

      10.1097/ccm.0b013e3182711972

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] n3/n6不飽和脂肪酸を主成分とする脂肪製剤の樹状細胞を介する免疫応答に与える差異2014

    • Author(s)
      大田典之
    • Organizer
      第41回日本集中治療医学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
    • Invited

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Published: 2014-07-25   Modified: 2019-07-29  

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