부산대학교 도서관

Nuclear factor κB (NFκB) plays a pivotal role in the coordinated transactivation of a series of genes of cytokines and adhesion molecules that are highly involved in the onset of acute rejection in organ transplantation. We previously developed decoy cis-elements oligo deoxyribonucleic acid against NFκB (NFκB-decoy) that effectively inhibited the activation of major inflammatory mediators in vitro and in vivo. Accordingly, we hypothesized that transfection of NFκB-decoy into the donor kidney would prevent acute rejection and prolong graft survival, and thus provide effective therapy for renal acute rejection. To transfect NFκB-decoy, we employed a novel approach using ultrasound exposure with an echocardiographic contrast agent, Optison, and clearly demonstrated successful transfection of NFκB-decoy into renal tissue. The therapeutic effect of NFκB-decoy on renal allografts was then evaluated in a rat renal allograft model (Wistar-Lewis). In the control group, graft function significantly deteriorated with marked destruc- tion of renal tissue, accompanied by increased production of major inflammatory mediators, and all animals died of renal failure by 9 days. In contrast, graft function (serum creatinine on day 2, NFκB-treated: 0.97 ± 0.16 versus control: 1.84 ± 0.23 mg/dl, P < 0.01) and histological structure were well preserved with significantly decreased expression of NFκB-regulated cytokines and adhesion molecules, including IL-1, iNOS, MCP-1, TNF-α, and ICAM-1, in allografts transfected with NFκB-decoy. As a result, animal survival was significantly prolonged in this group as compared to controls (14.2 ± 5.2 versus 7.1 ± 1.2 days, P < 0.01). Thus, we established a novel ultrasound-Optison-mediated gene transfection approach and demonstrated the significant prolongation of graft survival by the successful transfection of NFκB-decoy into the donor... [ABSTRACT FROM AUTHOR]