核转录因子-κB通路在CD40-CD154诱导血管内皮细胞活化中的作用  

Role of NF-κB pathway in CD40-CD154 interaction-induced human aortic endothelial cell activation

作　　者：朱彬[1] 王璞[1] 刘子栋[2] 吴春玲[1] 高庆贞[1] 王少梅[1] 徐何[2] 

机构地区：[1]山东大学附属济南市中心医院移植科,250013 [2]山东大学附属济南市中心医院移植科移植免疫研究室,250013

出　　处：《中华器官移植杂志》2008年第4期204-207,共4页Chinese Journal of Organ Transplantation

摘　　要：目的探讨血管内皮细胞（VEC）内核转录因子-κB（NF-κB）通路在CD40-CD154相互作用诱导VEC活化中的作用。方法应用重组人肿瘤坏死因子α（rhTNF-α）和重组人γ干扰素（rhIFN-γ）刺激人主动脉VEC，通过流式细胞仪（FACS）检测CD40和粘附因子表达水平；通过表达CD154的细胞株D1．1和VEC共同培养后，观察VEC粘附因子的表达水平；通过抗CD154单克隆抗体阻断CD40-CD154间的反应；应用NF-κB阻断剂BAY11-7082观察阻断NF-κB通路后对CD40-CD154诱导VEC活化的影响。结果未活化的VEC膜表达低水平的CD40、CD54和CD106，但不表达CD62E，经白细胞介素刺激后可上调这些蛋白分子的表达水平。D1．1细胞株和VEC共同培养后可诱导VEC活化并上调CD62E、CD54和CD106的表达水平；抗CD154抗体可阻断CD40-CD154间的反应所诱导的VEC活化；NF-κB阻断剂可阻断rhTNF-α诱导的VEC活化以及CD40-CD154间的反应所诱导的VEC活化。结论VEC中CD40和T淋巴细胞中CD154之间的相互作用在诱导VEC活化过程中起重要作用；CD40-CD154相互作用并通过NF-κB通路诱导VEC活化；NF-κB通路阻断剂可抑制VEC活化。Objective To determine human endothelial cells （VEC） activation induced by CD40- CD154 interaction and the role of NF-κB pathway in CD40-CD154 interaction. Methods VEC were isolated from aorta, and subcultures were stimulated by recombinant human TNF-α（rhTNF-α） or IFN-γ （rhIFN-γ）. The expression of CD40 and adhesion molecules was detected by using flow cytometry. D 1. 1 cells expressing CD154 were co-incubated with VEC with or without CD154 specific monoclonal antibody, and the effects of CD40-CD154 interaction in induceding VEC activation were determined. In an additional study, BAY 11-7082, a NF-κB pathway inhibitor, was used to study whether CD40-CD154 interaction-induced VEC activation was NF-κB pathway-dependent. Results Resting VEC demonstrated weak expression of CD40, CD54 and CD106 but undetectable CD62E. VEC stimulated with rhTNF-α or rhINF-γ up-regulated the expression of CD40, CD62E, CD54 and CD106 respectively. VEC demonstrated up-regulation of CD62E, CD54 and CD106 after co-incubation with D 1.1 cells, and VEC activation induced by CD40-CD154 interaction was inhibited by CD154 specific monoclonal antibody. NF-κB could block the VEC activation induced by rhTNF-α stimulation or by CD40-CD154 interaction. Conclusions The interaction between VEC-derived CD40 and CD154 expressing T cells plays a critical role in VEC activation. Inhibition of NF-κB during CD40-CD154 interaction prevents VEC activation.

关 键 词：NF-ΚB 内皮细胞 CD40配体 CD154配体 移植 

分 类 号：R686[医药卫生—骨科学]