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KAKEN_15K08666seika.pdf
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Download
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:306.9 KB
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:Oct 31, 2019 |
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Total downloads since Oct 31, 2019 : 1064
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乾癬性掻痒症の新規マウス評価系の確立とヒスタミンH4受容体を標的とする治療戦略
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カンセンセイ ソウヨウショウ ノ シンキ マウス ヒョウカケイ ノ カクリツ ト ヒスタミン H4 ジュヨウタイ オ ヒョウテキ ト スル チリョウ センリャク
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Kansensei sōyōshō no shinki mausu hyōkakei no kakuritsu to hisutamin H4 juyōtai o hyōteki to suru chiryō senryaku
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Expression of precipitating factors of pruritus found in humans in an imiquimodinduced psoriasis mouse model
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山浦, 克典
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ヤマウラ, カツノリ
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Yamaura, Katsunori
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慶應義塾大学・薬学部 (芝共立) ・教授
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Research team head
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科研費研究者番号 : 10543069
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樋坂, 章博
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ヒサカ, アキヒロ
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Hisaka, Akihiro
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千葉大学・大学院薬学研究院・教授
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Research team member
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科研費研究者番号 : 80420206
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佐藤, 洋美
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サトウ, ヒロミ
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Satō, Hiromi
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千葉大学・大学院薬学研究院・講師
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Research team member
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科研費研究者番号 : 30506887
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大石, 信雄
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オオイシ, ノブオ
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Ōishi, Nobuo
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Collaborator
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2019
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科学研究費補助金研究成果報告書
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2018
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| Abstract |
我々は、IMQ誘発乾癬モデルマウスの掻痒評価時の至適条件を決定した。掻痒に関与する因子として病変組織のマスト細胞数およびMCP-6、掻痒伝達神経の伸長因子としてNGFやNT3、起痒ペプチド前駆体のPPEなどのmRNA発現が掻痒と相関性を示すことを明らかにした。
IMQ誘発乾癬モデルマウスの皮膚病変形成に対し、選択的ヒスタミンH4受容体拮抗薬が有効性を示したことから、H4受容体が掻痒においても標的になり得ると考えたが、掻痒に対する同拮抗薬およびH4受容体欠損マウスを用いた検討から、H4受容体を乾癬性掻痒症治療の標的とすることは困難であることを明らかにした。
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.
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研究種目 : 基盤研究 (C) (一般)
研究期間 : 2015～2018
課題番号 : 15K08666
研究分野 : 薬学
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