Zinc oxide particles induce inflammatory responses in vascular endothelial cells via NF-κB signaling.
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.
Tsou
Tsui-Chun
TC
Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan. tctsou@nhri.org.tw
Yeh
Szu-Ching
SC
Tsai
Feng-Yuan
FY
Lin
Ho-Jane
HJ
Cheng
Tsun-Jen
TJ
Chao
How-Ran
HR
Tai
Lin-Ai
LA
D016923:Cell Death; D049109:Cell Proliferation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D005978:Glutathione / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016328:NF-kappa B / Q000378:metabolism*; D053758:Nanoparticles; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D015034:Zinc Oxide / Q000494:pharmacology*
D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; D005978:Glutathione; D015034:Zinc Oxide