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Cyclosporin A inhibits the adhesion of neutrophil with ECV-304 induced by hypoxia/reoxygenation via ROS-Cyclophilin A-ERK1/2 pathway
Author(s): 
Pages: 313-320
Year: Issue:  3
Journal: ACTA PHYSIOLOGICA SINICA

Keyword:  缺氧细胞粘附分子环孢霉素A亲环素A细胞外信号调节激酶;
Abstract: 为研究环孢霉素A(cyclosporin A,CsA)对缺氧/复氧诱导人脐静脉内皮细胞(ECV-304)与中性粒细胞粘附的影响,本工作以缺氧/复氧诱导粘附为模型,采用β-N-乙酰氨基己糖苷酶比色法检测粘附率,流式细胞术检测ECV-304细胞表面粘附分子E-选择素(E-selectin)、细胞间粘附分子-1(ICAM-1)的表达,Fenton反应测定活性氧(reactive oxygen species,ROS)的含量,West-em-blot法检测ECV-304细胞亲环素A(cyclophilinA,CyPA)、磷酸化及总细胞外信号调节激酶(ERK1/2)蛋白的表达.结果发现,ECV-304细胞经缺氧/复氧处理后,ROS释放增多,E-selectin、ICAM-1的表达上调,其表面中性粒细胞的粘附增加,CsA能显著抑制缺氧/复氧的上述作用.缺氧/复氧后,CyPA蛋白表达明显上调,ERK1/2显著活化,细胞总ERK1/2蛋白表达无明显改变.CyPA抑制剂CsA以及CyPA反义寡核苷酸均明显减轻缺氧/复氧诱导的ERK1/2激活,显著减少ECV-304细胞与中性粒细胞粘附.ERK1/2信号通路特异性阻断剂PD98059亦显著抑制ECV-304细胞与中性粒细胞的粘附.上述结果提示,CsA抑制缺氧/复氧诱导的ECV-304细胞与中性粒细胞粘附,并可能通过抑制ROS-Cyclophilin A-ERK1/2的信号转导途径实现.
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