RESUMEN
Our previous studies found that zinc oxide (ZnO) particles induced expression of intercellular adhesion molecule-1 (ICAM-1) protein in vascular endothelial cells via NF-κB and that zinc ions dissolved from ZnO particles might play the major role in the process. This study aimed to determine if zinc ions could cause inflammatory responses in a human promonocytic leukemia cell line HL-CZ. Conditioned media from the zinc-treated HL-CZ cells induced ICAM-1 protein expression in human umbilical vein endothelial cells (HUVEC). Zinc treatment induced chemokine and inflammatory cytokine release from HL-CZ cells. Inhibition of NFκB activity by over-expression of IκBα in HL-CZ cells did not block the conditioned medium-induced ICAM-1 protein expression in HUVEC cells. Zinc treatment induced activation of multiple immune response-related transcription factors in HL-CZ cells. These results clearly show that zinc ions induce chemokine and inflammatory cytokine release from human promonocytes, accompanied with activation of multiple immune response-related transcription factors. Our in vitro evidence in the zinc-induced inflammatory responses of vascular cells provides a critical linkage between zinc exposure and pathogenesis of those inflammatory vascular diseases.
Asunto(s)
Quimiocinas/metabolismo , Molécula 1 de Adhesión Intercelular/biosíntesis , Células Precursoras de Monocitos y Macrófagos/efectos de los fármacos , Células Precursoras de Monocitos y Macrófagos/inmunología , Zinc/toxicidad , Adenoviridae/genética , Secuencia de Bases , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Quimiocinas/genética , Medios de Cultivo Condicionados , Citocinas/genética , Citocinas/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/inmunología , Genes Reporteros , Células Endoteliales de la Vena Umbilical Humana , Humanos , Luciferasas de Luciérnaga/genética , Datos de Secuencia Molecular , Células Precursoras de Monocitos y Macrófagos/metabolismo , Factores de Transcripción/genética , Acetato de Zinc/toxicidadRESUMEN
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.