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The endoplasmic reticulum stress inducer thapsigargin enhances the toxicity of ZnO nanoparticles to macrophages and macrophage-endothelial co-culture

文献类型： 外文期刊

作者： Chen, Gui;Shen, Yuexin;Li, Xiyue;Jiang, Qin;Cheng, Shanshan;Gu, Yuxiu;Cao, Yi;Liu, Liangliang

作者机构：

关键词： THP-1 macrophages;Human umbilical vein endothelial cells (HUVECs);Co-culture;ZnO nanoparticles (NPs);Thapsigargin (TG)

期刊名称： ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY

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年卷期：

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收录情况： SCI

摘要： It was recently shown that exposure to ZnO nanoparticles (NPs) could induce endoplasmic reticulum (ER) stress both in vivo and in vitro, but the role of ER stress in ZnO NP induced toxicity remains unclear. Because macrophages are sensitive to ER stress, we hypothesized that stressing macrophages with ER stress inducer could enhance the toxicity of ZnO NPs. In this study, the effects of ER stress inducer thapsigargin (TG) on the toxicity of ZnO NPs to THP-1 macrophages were investigated. The results showed that TG enhanced ZnO NP induced cytotoxicity as revealed by water soluble tetrazolium-1 (WST-1) and neutral red uptake assays, but not lactate dehydrogenase (LDH) assay. ZnO NPs dose-dependently enhanced the accumulation of intracellular Zn ions without the induction of reactive oxygen species (ROS), and the presence of TG did not significantly affect these effects. In the co-culture, exposure of THP-1 macrophages in the upper chamber to ZnO NPs and TG significantly reduced the viability of human umbilical vein endothelial cells (HUVECs) in the lower chamber, but the release of tumor necrosis factor alpha (TNF alpha) was not induced. In summary, our data showed that stressing THP-1 macrophages with TG enhanced the cytotoxicity of ZnO NPs to macrophages and macrophage-endothelial co-cultures. (C) 2017 Elsevier B.V. All rights reserved.

分类号： R9

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