铁调素对NF-κB介导血管内皮细胞炎症反应的影响

INFLUENCE OF HEPCIDIN ON INFLAMMATION OF VASCULAR ENDOTHELIA INDUCED BY NF-κB

目的探讨铁调素(hepcidin)对血管内皮细胞(vascular endothelial cell,VEC)炎症通路中核转录因子κB(Nuclear Factor-κB,NF-κB)家族的影响。方法使用不同浓度的人铁调素处理人脐静脉内皮细胞(human umbilical vein endothelial cell;HUVEC)24h后,利用蛋白印迹技术(Western blot)检测细胞中核转录因子κB抑制蛋白α(inhibitor of NF-κB;IκBα)、细胞间粘附分子(intercellular adhesion molecule-1,ICAM-1)的蛋白表达;免疫荧光法观察NF-κB p65转核、ICAM-1蛋白表达;体外粘附实验检测干预后的HUVEC的粘附能力。结果铁调素能剂量依赖的降低HUVEC中IκBα及促进ICAM-1表达,其中干预剂量大于300 ng/ml处理组时的相比对照组差异均具有统计学意义(P<0.05);激光共聚焦成像结果显示,600 ng/ml铁调素处理24h后,HUVEC中NF-κB p65转入核内,ICAM-1蛋白表达增加;粘附实验的结果显示,剂量量大于75 ng/ml铁调素处理能剂量依赖性的上调HUVEC的粘附能力,与对照组相比差异均具有统计学意义(P<0.05)结论铁调素可诱导血管内皮细胞IκBα的下调,促使NF-κB p65转核,升高血管内皮细胞ICAM-1的表达水平。铁调素可通过调控NF-κB通路介导血管内皮细胞炎症反应。[营养学报,2014,36(1):31-34]

Objective To explore the influence of hepcidin on Nuclear Factor-κB （NF-κB） family in the vascular endothelial cell （VEC） inflammation signaling pathways. Methods After treatment of human umbilical vein endothelial cells （HUVECs） by different concentrations of human hepcidin for 24h, the expression of inhibitor of NF-κB （IκBα） and intercellular adhesion molecule-1 （ICAM-1） were determined by Western blotting. Nuclear translocation of p65 and the expression of ICAM-1 were identified by immunofluorescence stain. Adhesion capacity of HUVECs was observed in adhesion experiment. Results Hepcidin treatment could result in IκBα down-regulation and ICAM-1 up-regulation in dose-dependent manner, and significant difference was found for the concentrations more than 300 ng/ml （P〈0.05）. The observation zondee confocal laser scanning microscope indicated nuclear translocation of p65 and enhanced ICAM-1 expression when incubated with 600 ng/ml hepcidin. Adhesion experiment showed that adhesion capacity of HUVECs was increased in dose-dependent manner, Conclusion Human hepcidin induces IκBα down-regulation, promote nuclear translocation of NF-κB p65, and increase the level of ICAM-1 in HUVECs. Hepcidin can influence inflammation in vascular endothelial ceils through regulating the NF-κB signaling pathways.