2002 Fiscal Year Final Research Report Summary
The effect and mechanism of Vitamin-D analog on induction of transplant tolerance
| Project/Area Number |
13671418
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Fukuoka University |
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Principal Investigator |
IWASAKI Akinori Fukuoka University, School of Medicine, Lecturer, 医学部, 講師 (50248506)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAISHI Takeshi Fukuoka University, School of Medicine, Lecturer, 医学部, 講師 (10216179)
KAWAHARA Katsunobu Fukuoka University, School of Medicine, Associate Professor, 医学部, 助教授 (80152990)
SHIRAKUSA Takayuki Fukuoka University, School of Medicine, Professor, 医学部, 教授 (20038863)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Transplantation / Rejection / Lung / Janus Kinase 3 / Inter leukin 2 / Tyrphostin |
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| Research Abstract |
This project was primarily entitled as "The effect and mechanism of Vitamin-D analog on induction of transplant tolerance" expecting the Vitamin-D analog inhibit the costimulation signal (2nd signal) between antigen presenting cell and helper T cell during acute rejection. However, our preliminary investigation using rat lung transplant model revealed that the effect of Vitamin-D analog on suppression of acute rejection was insufficient. Thus we changed the project to investigate the effect of Tyrphostin AG490, a selective inhibitor of the JAK3/STAT pathway, on suppression of lung acute rejection.
Janus kinase 3 (Jak 3) is a cytoplasmic tyrosine kinase activated by cytokines that utilize the common interleukin-2 receptor gamma chain, such as IL-2, 4, 7, 9, 13, and 15. This pathway is named as 3rd signal on proliferation of effector T cell on allograft rejection. We examined the effects of the tyrosine kinase inhibition by Tyrosine AG490 using rat lung allograft model.
Our investigation demonstrated that AG 490, injected at a dose of 10-20mg/kg daily intraperitoneally, effectively suppressed rat lung allograft rejection pathologically and radiographically. Additionally, the effect of AG490 was shown to be dose dependent. Flow cytometric analysis of BALF (bronchio-alveolar lavage fluid) lymphocyte between no treatment recipient and AG490 recipient revealed that Th1/Th2 cytokine production was suppressed by AG490.
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