Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts
Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts
复制标题
针对核因子-κ B 的诱饵可减弱小鼠同种异体心脏移植物中的心肌细胞浸润和动脉新内膜形成
作者：
J. Suzuki;R. Morishita;Jun Amano;Y. Kaneda;M. Isobe;M. Isobe
心脏移植急性排斥反应和移植物动脉病变限制了受者的长期生存；这些过程被一些细胞因子和粘附分子增强。核因子κB （NFκB）在炎症和细胞增殖的多个基因的转录中起关键作用。为了验证NFκB诱骗剂可以减轻急性排斥反应和动脉病变的假设，我们采用日本血凝病毒(HVJ)-人工病毒包膜(AVE)-脂质体方法将NFκB诱骗剂单次腔内递送到小鼠同种异体心脏移植物中。没有进行诱饵或干扰诱饵转移来进行控制。从BALB/c小鼠移植到C3H/He小鼠（主要错配组），从DBA/2移植到B10。D2小鼠（轻微错配组）。主要错配组未处理或打乱诱饵转染的同种异体移植物急性排斥，而NFκB诱饵延长了其存活时间。轻微错配组的同种异体移植物在第28天出现严重的细胞浸润和内膜增厚，炎症因子增强，NFκB诱捕剂减轻了这些变化。我们得出结论，NFκB在移植心脏急性和慢性排斥反应的发展中起关键作用。NFκB诱骗物通过阻断几个基因的激活来减轻急性排斥反应和移植物动脉病变。
Acute rejection and graft arteriopathy in cardiac transplantation limit the long-term survival of recipients; these processes are enhanced by several cytokines and adhesion molecules. Nuclear factor-kappa B (NFκB) is critical in the transcription of multiple genes involved in inflammation and cell proliferation. To test the hypothesis that NFκB decoy can attenuate acute rejection and arteriopathy, we performed single intraluminal delivery of NFκB decoy into murine cardiac allografts using a hemagglutinating virus of Japan (HVJ)-artificial viral envelope (AVE)-liposome method. No decoy or scrambled decoy transfer was performed for control. Hearts were heterotopically transplanted from BALB/c to C3H/He mice (major mismatch group) and from DBA/2 to B10.D2 mice (minor mismatch group). Nontreated or scrambled decoy transfected allografts of the major mismatch group were acutely rejected, while NFκB decoy prolonged their survival. While severe cell infiltration and intimal thickening with enhancement of inflammatory factors were observed in untreated or scrambled decoy-treated allografts of minor mismatch group at day 28, NFκB decoy attenuated these changes. We conclude that NFκB is critically involved in the development of acute as well as chronic rejection of the transplanted hearts. NFκB decoy attenuates both acute rejection and graft arteriopathy by blocking the activation of several genes.
DOI：
10.1073/pnas.92.13.5855
发表时间：
1995-06-20
影响因子：
11.1
作者：
MORISHITA, R;GIBBONS, GH;DZAU, VJ
通讯作者：
DZAU, VJ