2001 Fiscal Year Final Research Report Summary
Tolerance induction by suppressing NF-KB activation
Project/Area Number |
11671178
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General surgery
|
Research Institution | Nara Medical-University |
Principal Investigator |
HISANAGA Michiyoshi Nara Medical Univ, Facurty of Medicine, Associate Professor., 医学部, 講師 (30275341)
|
Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Yoshiyuki Nara Medical Univ, Facurty of Medicine, Professor, 医学部, 教授 (00142381)
|
Project Period (FY) |
1999 – 2001
|
Keywords | Lirer / Ischemic injury / NF-KB / I-KB / Adeno virus / gene transfection |
Research Abstract |
Nuclear factor-kappa B (NF-kB) regulates various inflammatory cytokines, adhesion molecules, chemokines as well as growth factors that play important roles in organ transplantation. In this study, we planned to induce post transplantation tolerance by controlling NF-kB activation using rat cardiac allo-transplantation model. "Decoy oligodeoxynucleotides", which shares the same kB sequences in nuclear NF-kB binding site, was transected into donor heart as well as recipient using HVJ-liposome. However, transfection was not successful by X-Gal staining, although a lot of trials were attempted. Then we have changed strategies targeting different organs and animal species, I.e., human I-kB adenovirus using CMV promoter (AdCMVhIkB) was transected into mouse liver using hepatic ischemia-reperfusion model. 48 hours before hepaticischemia, 1x10^9 pfu AdCMVhIkB was intraportally injected. Suppression of NF-kB activation as well as I-kB over expression was recognized before ischemia however, significant protective effect was not found so far. Furtherinvestigations concerning dministration sites, timing, and vector numbers are necessary.
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