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Expression of precipitating factors of pruritus found in humans in an imiquimodinduced psoriasis mouse model

Research Project

Project/Area Number 15K08666
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pain science
Research InstitutionKeio University

Principal Investigator

Yamaura Katsunori  慶應義塾大学, 薬学部(芝共立), 教授 (10543069)

Co-Investigator(Kenkyū-buntansha) 佐藤 洋美  千葉大学, 大学院薬学研究院, 講師 (30506887)
樋坂 章博  千葉大学, 大学院薬学研究院, 教授 (80420206)
Research Collaborator OISHI nobuo  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsイミキモド(IMQ)誘発乾癬モデルマウス / 掻痒 / SCLABA-Real / マスト細胞 / Mast cell protease-6 / Nerve growth factor / Neurotrophin 3 (NT3) / Preproenkephalin (PPE) / 掻破回数 / NGF / TSLP / Preproenkephalin / H4受容体アンタゴニス / イミキモド(IMQ)乾癬マウス / NGF mRNA / H4R KOマウス / H4受容体アンタゴニスト / 耳介腫脹スコア / 肥厚スコア / イミキモド(IMQ) / 乾癬 / ヒスタミン / 皮膚炎
Outline of Final Research Achievements

Topical application of imiquimod increased the Psoriasis Area and Severity Index score as well as the frequency and duration of self-scratching. Regarding internal factors, increases in mast cells number and mRNA expression of nerve growth factor (NGF) and endogenous pruritogenic peptide precursor were confirmed. Self-scratching behavior is accompanied by increased number of mast cells and expression of NGF and endogenous pruritogenic peptides in our imiquimod-induced psoriasis model.
Furthermore, we confirmed that histamine H4 receptor doesn't have an important role on the pruritus of an imiquimod-induced psoriasis model by the investigation using specific H4 receptor antagonists and H4 receptor knockout mice.

Academic Significance and Societal Importance of the Research Achievements

掻痒を伴う乾癬患者において発現が亢進していることが報告されている複数の因子が、我々が用いたIMQ誘発乾癬モデルマウスにおいても同様に増加していた。さらに、これらの因子とマウスの掻痒反応の間に相関性が示されたことから、本モデルマウスは掻痒を伴う乾癬患者を忠実に模倣していると考えられた。今後、乾癬性掻痒症治療薬の薬効評価および掻痒の病態解明に応用し、医療に貢献出来ると考えられる。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (7 results)

All 2017 2016 2015

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] 特集痒みのメカニズム2016 V. ステロイド外用薬が誘発する痒み2016

    • Author(s)
      山浦克典、船越彩花
    • Journal Title

      アレルギー・免疫

      Volume: 8 Pages: 38-47

    • Related Report
      2016 Research-status Report
  • [Journal Article] Protective Effect of Young Green Barley Leaf (Hordeum vulgare L.) on Restraint Stress-Induced Decrease in Hippocampal BDNF in Mice.2015

    • Author(s)
      Katsunori Yamaura, Riho Tanaka, Yuanyuan Bi, Hideki Fukata, Nobuo Oishi, Hiromi Sato, Chisato Mori, Koichi Ueno.
    • Journal Title

      Pharmacognosy Magazine

      Volume: 11 Issue: 42 Pages: 86-86

    • DOI

      10.4103/0973-1296.157702

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Effect of enhanced expression of connexin 43 on sunitinib-induced cytotoxicity in mesothelioma cells.2015

    • Author(s)
      Miaki Uzu, Hiromi Sato, Ryota Yamada, Tatsuro Kashiba, Yukihiro Shibata, Katsunori Yamaura, Koichi Ueno.
    • Journal Title

      J Pharmacol Sci.

      Volume: 128 Issue: 1 Pages: 17-26

    • DOI

      10.1016/j.jphs.2015.04.002

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Elacridar enhances the cytotoxic effects of sunitinib and prevents multidrug resistance in renal carcinoma cells.2015

    • Author(s)
      Hiromi Sato, Sana Siddig, Miaki Uzu; Sayumi Suzuki; Yuki Nomura; Tatsuro Kashiba; Keisuke Gushimiyagi; Yuko Sekine, Tomoya Uehara, Yasushi Arano, Katsunori Yamaura, Koichi Ueno.
    • Journal Title

      Eur. J. Pharmacol.

      Volume: 746 Pages: 258-266

    • DOI

      10.1016/j.ejphar.2014.11.021

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] イミキモド誘発乾癬モデルマウスにおける掻破行動解析および掻痒誘発関連因子の探索2017

    • Author(s)
      大石信雄、岩田 紘樹、小林 典子、藤本 和子、佐藤 洋美、樋坂 章博、山浦 克典
    • Organizer
      2017年日本免疫毒性学会 第24回年会
    • Related Report
      2017 Research-status Report
  • [Presentation] Long-term topical steroid therapy can be a probable cause for pruritus.2015

    • Author(s)
      Yamaura K.
    • Organizer
      8th World Congress on Itch.
    • Place of Presentation
      Nara Kasugano International Forum IRAKA, Nara, Japan
    • Year and Date
      2015-09-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Topical application of DP1 agonist effectively prevents pruritus induced by long-term treatment of glucocorticoids in allergic contact dermatitis mice.2015

    • Author(s)
      Ayaka Funakoshi, Katsunori Yamaura, Seiji Onuma, Riho Tanaka, Misako Takei, Naotomo Kambe, Hiromi Sato, Akihiro Hisaka.
    • Organizer
      8th World Congress on Itch.
    • Place of Presentation
      Nara Kasugano International Forum IRAKA, Nara, Japan
    • Year and Date
      2015-09-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2020-03-30  

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