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

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K08666
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Keio 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
• 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)

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.

Free Research Field

薬学

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。