| Project/Area Number |
16K08409
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | International University of Health and Welfare |
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Principal Investigator |
YAGI HIDEKI 国際医療福祉大学, 薬学部, 教授 (40250740)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | FTY720 / S1P / 抗体 / 接触性過敏症 / アレルギー性皮膚炎 / S1PR / スフィンゴシン 1-リン酸（S1P） / モノクローナル抗体 / フィンゴリモド / 接触性皮膚炎 / スフィンゴシン1－リン酸（S1P） / スフィンゴシン 1-リン酸 / S1PR4 / 免疫学 / アレルギー・ぜんそく / 脂質 |
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| Outline of Final Research Achievements |
For the purpose of clinical adaptation expansion of Fingolimod (FTY720) used as a therapeutic drug of the multiple sclerosis. We examined it in an animal model of oxazolone-induced contact hypersensitivity. Anti-inflammation effect to contact hypersensitivity was accepted by oral administration of 1 mg/kg of FTY720. This drug inhibited both effector T cell and dermis dendritic cell egress from the draining lymph node to the inflammatory lesion. On the other hand, the sphingosine 1-phosphate receptors (S1PR) considered to be target molecules of FTY720. The monoclonal antibody against mouse S1P4 were not available. We tried the production of anti-mouse S1P4 monoclonal antibody. We established three GFP-fusion mouse S1P4 receptor-expressing cells for immune cells. The rats were immunized by the mouse S1P4-expressing RH7777 cells. The antiserum of the immune rats got highly titer against mouse S1P4. However, we could not select hybridoma producing to mouse S1P4 monoclonal antibody.
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| Academic Significance and Societal Importance of the Research Achievements |
多発性硬化症の治療薬として用いられるフィンゴリモド（FTY720）の臨床適応拡大を目的に、アレルギー性接触性皮膚炎の動物モデルで、FTY720の1 mg/kgの経口投与で治療効果が認められた。これは、フィンゴリモドが細胞移動を伴うⅣ型アレルギーへの適用拡大ができる可能性を示したものである。メカニズムもエフェクターT細胞や真皮樹状細胞を感作付近のリンパ節にとどめ、炎症局所への移動を抑制することが示唆され、作用機序との整合性もあり、有望と考える。
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