Functional mechanism of cyclosporin A therapy for immunoglobulin-resistant Kawasaki disease
| Project/Area Number |
24591584
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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 |
Pediatrics
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIKAWA Norishige 和歌山県立医科大学, 医学部, 教授 (10158412)
SUZUKI Hiroyuki 和歌山県立医科大学, 医学部, 准教授 (80196865)
SUENAGA Tomohiro 和歌山県立医科大学, 医学部, 助教 (70433365)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 難治性川崎病 / シクロスポリンA / NFAT / ITPKC / CASP3 / 川崎病 / NFAT経路 / 細胞内シグナル伝達 / T細胞 / シクロスポリン / IVIG不応 |
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| Outline of Final Research Achievements |
The functional mechanism of CsA therapy in KD patients has remained unclear. To evaluate the NFAT pathway and activation of JAK and STAT pathway, we examined the gene expression using real-time RT-PCR and, pSTAT3 and pSTAT5 using flow cytometry. Thirty-six KD patients were divided into three groups: responsive to initial IVIG, responsive to additional IVIG, and treated with CsA group. In the CsA group, expression of mRNAs for interleukin-2 NFATc1 and NFATc2 was significantly increased, whereas the mean fluorescence intensity (MFI) of pSTAT3 (CD3+ T cell) and pSTAT3 (CD16b+ granulocyte) was decreased after CsA treatment. In the group responsive to initial IVIG, the expression of mRNAs for STAT3, 5A, 5B was decreased after IVIG treatment; on the other hand, the MFI of pSTAT3 (CD3+ T cell) and pSTAT3 (CD16b+ granulocyte) was decreased, and that of pSTAT5 (CD16b+ granulocyte) was increased, after IVIG. Our results suggest that CsA may act through a mechanism other than the NFAT pathway.
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Report
(4 results)
Research Products
(29 results)
