Tolerance induction by suppressing NF-KB activation

通过抑制 NF-KB 激活诱导耐受

• 批准号: 11671178
• 负责人: HISANAGA Michiyoshi
• 金额: $ 2.24万
• 依托单位: Nara Medical-University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671178/
• 关键词: Lirer; Ischemic injury; NF-KB; I-KB; Adeno virus; gene transfection; 異所性心移植; 拒絶反応; HVJ-リポゾーム

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.

核因子-kappa B (NF-kB) 调节各种炎症细胞因子、粘附分子、趋化因子以及生长因子，在器官移植中发挥重要作用。在这项研究中，我们计划使用大鼠心脏同种异体移植模型控制 NF-kB 激活来诱导移植后耐受。 “诱饵寡脱氧核苷酸”在核 NF-kB 结合位点具有相同的 kB 序列，使用 HVJ 脂质体将其横切到供体心脏以及受体中。然而，尽管尝试了很多试验，但通过X-Gal染色转染并不成功。然后我们改变了针对不同器官和动物物种的策略，即利用肝缺血再灌注模型将使用CMV启动子的人I-kB腺病毒（AdCMVhIkB）横切到小鼠肝脏中。肝缺血前48小时，门静脉内注射1x10^9 pfu AdCMVhIkB。在缺血之前就发现了 NF-kB 激活和 I-kB 过度表达的抑制，但迄今为止尚未发现显着的保护作用。 Furtherinvestigations concerning dministration sites, timing, and vector numbers are necessary.