| Project/Area Number |
15591472
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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 | Osaka University |
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Principal Investigator |
SHIONO Hiroyuki Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20346216)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUDA Hikaru Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00028614)
MINAMI Masato Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10240847)
太田 三徳 大阪大学, 医学系研究科, 講師 (30203805)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | lung transplantation / MHC / graft rejection / immunosuppression / rat / HVJ / MHC class II / CIITA / 遺伝子導入 / 遺伝子導 |
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| Research Abstract |
Inhibition of the graft rejection is essential for the successful organ transplantation. Although the improvement of immunosuppressants have been made the transplantation safer, more effective methods for the control of rejection are still needed.
Our novel strategy for the control of the graft rejection is to down-regulate the expression of MHC class II molecules in the transplanted organs by interfering the function of MHC class II transactivator (CIITA), which is one of the transcription factor of MHC molecules.
A deletion mutant protein which express only the biding domain is supposed to work as a dominant negative mutation and to suppress the expression of MHC class II molecules. Dominant mutant cDNA was introduced into Raji cells, the B cell line expressing HLA-DR. Expression of HLA-DR antigen was shown to be significantly suppressed in the stable transfectants.
Hemagglutinating virus of Japan (HVJ virus) envelope vector with cDNA was amplified, and infused via a catheter which was inserted into the vein dorsalis penis superficiales of rats. The expression of the protein of inserted cDNA was clearly detected in the alveolar in the rat lungs.
These achievement should enable us to develop the rat donor lungs in which HLA class II molecules are down-regulated for the inhibition of the rejection. This novel strategy for the control of the rejection could be useful against any sorts of organ transplants.
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