Study of the mechanisms of action of calcineurin inhibitors on Kawasaki disease-like coronary arteritis
Project/Area Number |
16K19652
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Pediatrics
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Research Institution | Kyushu University |
Principal Investigator |
Murata Kenji 九州大学, 医学研究院, 共同研究員 (70770642)
|
Project Period (FY) |
2016-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
Keywords | カルシニューリン阻害薬 / 川崎病 / 冠動脈炎 / 自然免疫 / MyD88 / マウスモデル / 血管炎 / 小児科 / 免疫抑制剤 |
Outline of Final Research Achievements |
Calcineurin inhibitors have been used for the treatment of refractory Kawasaki disease. However, the effect on coronary artery lesions in Kawasaki disease patients remains unknown. This study aimed to investigate the effects and the mechanisms of actions on Kawasaki disease-like coronary arteritis of calcineurin inhibitors. Calcineurin inhibitors exacerbated the Nod1-mediated coronary arteritis in a dose-dependent manner. Similar effects were obtained in SCID mice, suggesting that T and B cells were not essential. On the other hand, MyD88, adapter molecule downstream of Toll-like receptors, was essential for the exacerbation of arteritis due to calcineurin inhibitors. Furthermore, calcineurin inhibitors enhanced the expression of adhesion molecules by endothelial cells and the cytokine secretion by monocytic cells on MyD88 dependence.
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Report
(3 results)
Research Products
(4 results)