Article

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

Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan; Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University, Taipei, Taiwan; Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Neipu, Pingtung, Taiwan; Center for Nanomedicine Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
Journal of hazardous materials (Impact Factor: 4.14). 11/2010; DOI: 10.1016/j.jhazmat.2010.07.010

ABSTRACT 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 μg/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-κB reporter activity. Overexpression of IκBα completely inhibited ZnO-induced ICAM-1 expression, suggesting NF-κB 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-κB-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-κB signaling, which could have important implications for treatments of vascular disease.

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