Transcriptional and posttranscriptional regulation and endocytosis were involved in zinc oxide nanoparticle-induced interleukin-8 overexpression in human bronchial epithelial cells.

Inhaled zinc oxide nanoparticles (ZnO-NPs) can induce lung inflammation through released inflammatory mediators, such as interleukin 8 (IL-8), from airways. However, the mechanisms underlying ZnO-NP-induced IL-8 gene expression have not been fully characterized. The transcription inhibitor actinomycin D (Act D) and the BEAS-2B cells stably overexpressing wild-type or mutated IL-8 promoter at the NFκB or C/EBPβ binding site were used to determine the involvement of transcriptional mechanisms. The effect of ZnO-NPs on IL-8 mRNA stability was examined using mRNA decay assay. The phagocytosis inhibitor cytochalasin B (CB) was utilized to define the role of endocytosis in ZnO-NP-induced IL-8 expression. In addition, the solubility of ZnO-NPs in culture medium was assessed using atomic absorption spectroscopy. Exposure to ZnO-NPs significantly increased the expression of IL-8 mRNA and protein in a dose-dependent manner. Pretreatment with Act D blocked ZnO-NP-induced IL-8 expression. Both NFκB and C/EBPβ transcription factors were required for ZnO-NP-induced IL-8 transcription. mRNA decay assay showed that ZnO-NP stimulation delayed IL-8 mRNA degradation in BEAS-2B cells. Pretreatment of BEAS-2B cells with CB blocked ZnO-NP-induced IL-8 expression by 30 %. Exposure to ZnO-NPs induced IL-8 gene expression through transcriptional activation and mRNA stabilization. Internalization of nanoparticles was partially involved in ZnO-NP-induced IL-8 expression.