Elucidation of the onset mechanism of abacavir-induced severe skin reaction using humanized model animal
| Project/Area Number |
15K14995
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Chiba University |
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Principal Investigator |
Ito Kousei 千葉大学, 大学院薬学研究院, 教授 (30323405)
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| Co-Investigator(Kenkyū-buntansha) |
関根 秀一 千葉大学, 大学院薬学研究院, 講師 (70401007)
青木 重樹 千葉大学, 大学院薬学研究院, 助教 (30728366)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | HLA / 特異体質毒性 / 皮疹 |
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| Outline of Final Research Achievements |
There was no suitable animal model to reproduce the idiosyncratic toxicity related to HLA polymorphism. In order to reproduce the rash caused by abacavir (ABC) seen in HLA-B*57:01 polymorphic carriers, mice introduced with HLA-B*57:01 or its negative control (HLA-B*57:03 polymorphism) were prepared. ABC was applied to their skin in vivo or to their primary cultured keratinocytes in vitro to investigate specific immune response. As a result, increase in lymph node weight in vivo and acute induction of inflammatory cytokines in vitro were selectively observed only in B*57:01 mice group. Idiosyncratic immune response related to HLA polymorphism was reproduced for the first time in our transgenic mice model, and the possibility that HLA polymorphism-dependent acute cellular response might be involved in tissue-specific drug toxicity.
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Report
(3 results)
Research Products
(9 results)
