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 mu g/ml. ZnO concentrations of <= 3 mu g/ml resulted in increased cell proliferation, while those of <= 45 mu g/ml caused dose-dependent increases in oxidized glutathione levels. Treatments with ZnO concentrations <= 45 mu g/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-kappa B reporter activity. Overexpression of I kappa B alpha completely inhibited ZnO-induced ICAM-1 expression, suggesting NF-kappa B plays a pivotal role in regulation of ZnO-induced inflammation in HUVECs. Additionally. TNF-alpha, a typical inflammatory cytokine, induced ICAM-1 expression in an NF-kappa B-dependent manner, and ZnO synergistically enhanced TNF-alpha-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-kappa B signaling, which could have important implications for treatments of vascular disease. (C) 2010 Elsevier B.V. All rights reserved.