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Novel therapeutics for macrophage-driven inflammatory diseases via nicotinic acetylcholine receptor signaling

Research Project

Project/Area Number 15K10563
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionWakayama Medical University

Principal Investigator

Kishioka Shiroh  和歌山県立医科大学, 医学部, 教授 (60137255)

Co-Investigator(Kenkyū-buntansha) 雑賀 史浩  和歌山県立医科大学, 医学部, 助教 (10644099)
深澤 洋滋  関西医療大学, 保健医療学部, 准教授 (70336882)
Co-Investigator(Renkei-kenkyūsha) KIGUCHI Norikazu  和歌山県立医科大学, 医学部, 講師 (90433341)
Research Collaborator KOBAYASHI Daichi  和歌山県立医科大学, 医学部, 特別研究員
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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords慢性炎症 / マクロファージ / フェノタイプ / サイトカイン / ニコチン受容体 / 神経障害性疼痛 / α4β2 / ケモカイン / 神経炎症 / STAT3 / ニコチン性アセチルコリン受容体 / ミクログリア / ニコチン / 炎症
Outline of Final Research Achievements

We determined the effects of nicotinic acetylcholine receptor (nAChR) signaling on regulation of macrophage phenotypes that contribute to chronic inflammatory disease such as neuropathic pain. Macrophages underlying neuropathic pain express nAChR, and nAChR ligands suppressed the production of inflammatory mediators in vivo and in vitro. Moreover, it is important that administration of nAChR ligands improved neuropathic pain. In conclusion, regulation of inflammatory macrophages through nAChR signaling may be effective pharmacotherapy for the relief of chronic inflammatory diseases.

Report

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

    (9 results)

All 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (5 results)

  • [Journal Article] Inhibition of peripheral macrophages by nicotinic acetylcholine receptor agonists suppresses spinal microglial activation and neuropathic pain in mice with peripheral nerve injury2018

    • Author(s)
      Kiguchi N, Kobayashi D, Saika F, Matsuzaki S, Kishioka S
    • Journal Title

      J Neuroinflammation

      Volume: 15 Issue: 1 Pages: 96-96

    • DOI

      10.1186/s12974-018-1133-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacological Regulation of Neuropathic Pain Driven by Inflammatory Macrophages2017

    • Author(s)
      Kiguchi N, Kobayashi D, Saika F, Matsuzaki S, Kishioka S
    • Journal Title

      Int J Mol Sci

      Volume: 18 Issue: 11 Pages: 2296-2296

    • DOI

      10.3390/ijms18112296

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peripheral administration of interleukin-13 reverses inflammatory macrophage and tactile allodynia in mice with partial sciatic nerve ligation2017

    • Author(s)
      Kiguchi N, Sakaguchi H, Kadowaki Y, Saika F, Fukazawa Y, Matsuzaki S, Kishioka S
    • Journal Title

      J Pharmacol Sci

      Volume: 133 Issue: 1 Pages: 53-56

    • DOI

      10.1016/j.jphs.2016.11.005

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Altered expression of glial markers, chemokines, and opioid receptors in the spinal cord of type 2 diabetic monkeys2017

    • Author(s)
      Kiguchi N, Ding H, Peters CM, Kock ND, Kishioka S, Cline JM, Wagner JD, Ko MC
    • Journal Title

      Biochim Biophys Acta

      Volume: 1863 Issue: 1 Pages: 274-283

    • DOI

      10.1016/j.bbadis.2016.10.007

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] マクロファージ上で発現するα4β2ニコチン性アセチルコリン受容体活性化による神経障害性疼痛の緩和2017

    • Author(s)
      雑賀史浩、木口倫一、松﨑伸介、岸岡史郎
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 2型糖尿病発症カニクイザルの脊髄後角におけるケモカイン発現変動2017

    • Author(s)
      木口倫一、Huiping Ding、雑賀史浩、松﨑伸介、岸岡史郎、Mei-Chuan Ko
    • Organizer
      生理学研究所研究会「痛みの理解を目指した先端的アプローチ」
    • Place of Presentation
      岡崎
    • Year and Date
      2017-01-31
    • Related Report
      2016 Research-status Report
  • [Presentation] ニコチン性アセチルコリン受容体リガンドの末梢投与は神経障害性疼痛を改善する2017

    • Author(s)
      木口倫一、雑賀史浩、松﨑伸介、岸岡史郎
    • Organizer
      第5回ニューロカンファレンス和歌山
    • Place of Presentation
      和歌山
    • Year and Date
      2017-01-07
    • Related Report
      2016 Research-status Report
  • [Presentation] 傷害神経に浸潤するマクロファージは脊髄ミクログリアの活性化を調節する2017

    • Author(s)
      木口倫一、雑賀史浩、小林大地、松﨑伸介、岸岡史郎
    • Organizer
      第39回日本生物学的精神医学会・第47回日本神経精神薬理学会合同年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 神経傷害後の末梢マクロファージによる脊髄ミクログリア調節作用2017

    • Author(s)
      木口倫一、小林大地、雑賀史浩、松﨑伸介、岸岡史郎
    • Organizer
      第131回日本薬理学会近畿部会
    • Related Report
      2017 Annual Research Report

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

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