Zinc oxide particles induce inflammatory responses in vascular endothelial cells via NF-kB signaling

摘要

This study investigated inflammatory effects of zinc oxide (ZnO) particles on vascular endothelial cells. The effects of 50 and 100-nm ZnO particles on human umbilical vein endothelial cells (HUVECs) were characterized by assaying cytotoxicity. cell proliferation, and glutathione levels. A marked drop in survival rate was observed when ZnO concentration was increased to 45 μg/ml. ZnO concentrations of <3 μg/ml resulted in increased cell proliferation, while those of <45 |xg/ml caused dose-dependent increases in oxidized glutathione levels. Treatments with ZnO concentrations <45 μg/ml were performed to determine the expression of intercellular adhesion molecule-1 (ICAM-1) protein, an indicator of vascular endothelium inflammation, revealing that ZnO particles induced a dose-dependent increase in ICAM-1 expression and marked increases in NF-kB reporter activity. Overexpression of lkBα completely inhibited ZnO-induced ICAM-1 expression, suggesting NF-kB plays a pivotal role in regulation of ZnO-induced inflammation in HUVECs. Additionally, TNF-α, a typical inflammatory cytokine, induced ICAM-1 expression in an NF-KB-dependent manner, and ZnO synergistically enhanced TNF-α-induced ICAM-1 expression. Both 50 and 100-nm ZnO particles agglomerated to similar size distributions. This study reveals an important role for ZnO in modulating inflammatory responses of vascular endothelial cells via NF-kB signaling, which could have important implications for treatments of vascular disease.