摘要
目的探讨连环蛋白p120在炎性细胞因子肿瘤坏死因子-α(TNF-α)介导的肺微血管内皮细胞激活中的作用及其机制。方法使用小干扰RNA(siRNA)下调p120在内皮细胞中的表达,考察TNF-α刺激所引起的转录因子NF-κB激活、细胞间黏附因子ICAM-1表达水平,以及中性粒细胞跨内皮迁移能力;使用NF-κB特异性抑制剂明确p120对炎症性肺损伤的调节机制。结果 TNF-α能够降低内皮细胞p120的表达水平;p120下调加重了TNF-α介导的NF-κB激活、ICAM-1表达水平增高以及中性粒细胞跨内皮迁移,而NF-κB抑制剂则阻断了该效应。结论 p120通过抑制NF-κB活化,在TNF-α介导的肺微血管内皮细胞激活及随后的中性粒细胞跨内皮迁移中起重要的保护作用。
Objective To investigate the role of p120 catenin in inflammatory cytokine tumor necrosis factor-α（TNF-α）- induced lung microvascular endothelial cells activation, and explore the underlying mechanism. Methods p120 expres- sion level in endothelial cells was downregulated with specific p120 small interference RNA （siRNA）. Difference of TNF-α-induced nuclear factor-KB （NF-KB） activation, intracellular adhesion molecular-1 （ ICAM-1 ） expression, and neutrophil transendothelial migration were detected. Mechanism of p120＇s regulatory role in inflammatory lung injury with specific NF-KB inhibitor was investigated. Results TNF-α reduced p120 level in lung microvascular endothelial cells, p120 downregulation in endothelial ceils significantly aggravated TNF-α-induced NF-KB activation, ICAM-1 expression, and neutrophil transendothelial migration. These effects were remarkably suppressed by NF-KB inhibitor. Conclusion p120 plays a critical protective role in TNF-α-induced lung microvascular endothelial cells activation and subsequent neutrophil transendothelial migration through the inhibition of NF-KB activation.
出处
《山东大学学报（医学版）》
CAS
北大核心
2014年第12期41-44,49,共5页
Journal of Shandong University:Health Sciences
基金
国家自然科学基金青年科学基金(81100052)
山东省国际科技合作项目(26010104031205)
