Synergistic Effects of Calcineurin Inhibitors and Steroids on Steroid Sensitivity of Peripheral Blood Mononuclear Cells
| Project/Area Number |
23590201
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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 | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
平野 俊彦 東京薬科大学, 薬学部, 教授 (90173252)
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| Co-Investigator(Renkei-kenkyūsha) |
島津 元秀 (70124948)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ステロイド / 感受性 / カルシニューリン阻害薬 / ファーマコダイナミクス / 相互作用 / FKBP / タクロリムス / フォーマコダイナミクス / シクロスポリン / ステロイド感受性 / カルシニュリン阻害薬 / 薬力学的相互作用 / FKBP51 / FKBP52 / シクロフィリン40 |
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| Research Abstract |
The steroid receptor (SR) complex contains FKBP51 and FKBP52, which bind to tacrolimus (TAC) and cyclophilin 40, which in turn binds to cyclosporine (CYA); these influence the intranuclear mobility of steroid-SR complexes. Pharmacodynamic interactions are thought to exist between steroids and calcineurin inhibitors (CNIs) on the SR complex. We examined the effect of CNIs on steroid sensitivity. We examined the steroid sensitivity of mixed culture with both methylprednisolone (MPSL) and CNIs in 30 healthy subjects.and MPSL and cortisol sensitivity were examined before and after CNI administration in 23 renal transplant recipients.
Steroid sensitivity increased with both TAC and CYA. Furthermore, TAC had a greater effect on increasing sensitivity. Thus, concomitant administration of CNIs and steroid can increase steroid sensitivity. However, we could not have demonstrated the action mechanism, though we are resolving the action mechanism, using Jurkat cell knockdown FKBP51 with SiRNA
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Synergistic Effects of Calcineuri n Inhibitors and Steroids on Steroid Se nsitivity of Peripheral Blood Mononuclea r Cells2014
Author(s)
Hironori Takeuchi, Hitoshi Iwamoto, Yuki Nakamura, Toshihiko Hirano, Osamu Kon no, Yu Kihara, Naokazu Chiba, Takayoshi Yokoyama, Kiminori Takano, Tatsunori Toraishi, Kiyoshi Okuyama, Chie Ikeda, S achiko Tanaka, Kenji Onda, Akiko Soga, Yukiko Kikuchi, Takashi Kawaguchi, Shig eyuki Kawachi, Sakae Unezaki, Motohide Shimazu
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Journal Title
Cell Medicine
Volume: (accepted)
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[Journal Article] Steroid Withdrawal Based on Lymphocyte Sensitivity to Endogenous Cortisol in Renal Transplant Recipients2011
Author(s)
H Takeuchi, N Matsuno, T Hirano, M Gulimire, K Hama, Y Nakamura,H Iwamoto,T Kawaguchi, K Okuyama, S Unezaki, Nagao T
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Journal Title
Biol Pharm Bull
Volume: 34（10）
Pages: 1578-1583
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[Presentation] Synergistic Effect of Steroid Sensitiv ity to Peripheral Blood Mononuclear Cell s on Calcineurin Inhibitors2013
Author(s)
Hironori Takeuchi, Hitoshi Iwamoto, Yuki Nakamura, Osamu Konno, Yu Kihara, N aokazu Chiba, Takayoshi Yokoyama, Kimi nori Takano, Tatsunori Toraishi, Kiyoshi Okuyama, Sakae Unezaki, Toshihiko Hira no, Shigeyuki Kawachi, Motohide Shimaz u
Organizer
The 13 th C ongress of Asian Society of Transplanta tion
Place of Presentation
Kyoto
Year and Date
2013-09-03
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[Presentation] Synergistic Effect of Steroid Sensitivity to Peripheral Blood Mononuclear Cells on Calcineurin Inhibitors
Author(s)
Hironori Takeuchi, Hitoshi Iwamoto, Yuki Nakamura, Osamu Konno, Yu Kihara, Naokazu Chiba, Takayoshi Yokoyama, Kiminori Takano, Tatsunori Toraishi, Kiyoshi Okuyama, Sakae Unezaki, Toshihiko Hirano, Shigeyuki Kawachi, Motohide Shimazu
Organizer
The 13 th Congress of Asian Society of Transplantation
Place of Presentation
Kyoto
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