Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079, USA.
Nanomedicine (Lond). 2012 Jun;7(6):835-46. doi: 10.2217/nnm.11.154. Epub 2012 Feb 16.
The purpose of the current study was to determine whether copper nanoparticles (Cu-NPs) can induce the release of proinflammatory mediators that influence the restrictive characteristics of the blood-brain barrier.
MATERIAL & METHODS: Confluent rat brain microvessel endothelial cells (rBMECs) were treated with well-characterized Cu-NPs (40 or 60 nm). Cytotoxicity of the Cu-NPs was evaluated by cell proliferation assay (1.5-50 µg/ml). The extracellular concentrations of proinflammatory mediators (IL-1β, IL-2, TNF-α and prostaglandin E(2)) were evaluated by ELISA.
The exposure of Cu-NPs at low concentrations increases cellular proliferation of rBMECs, by contrast, high concentrations induce toxicity. Prostaglandin E(2) release was significantly increased (threefold; 8 h) for Cu-NPs (40 and 60 nm). The extracellular levels of both TNF-α and IL-1β were significantly elevated following exposure to Cu-NPs. The P-apparent ratio, as an indicator of increased permeability of rBMEC was approximately twofold for Cu-NPs (40 and 60 nm).
These data suggest that Cu-NPs can induce rBMEC, proliferation at low concentrations and/or induce blood-brain barrier toxicity and potential neurotoxicity at high concentrations.
本研究旨在确定铜纳米粒子（Cu-NPs）是否能引发促炎介质的释放，从而影响血脑屏障的限制特性。
用具有良好特性的 Cu-NPs（40 或 60nm）处理脑微血管内皮细胞（rBMECs）。用细胞增殖试验（1.5-50μg/ml）评估 Cu-NPs 的细胞毒性。通过 ELISA 评估促炎介质（IL-1β、IL-2、TNF-α和前列腺素 E（2））的细胞外浓度。
Cu-NPs 在低浓度下的暴露会增加 rBMECs 的细胞增殖，而高浓度则会诱导毒性。前列腺素 E（2）的释放明显增加（三倍；8h）Cu-NPs（40 和 60nm）。TNF-α和 IL-1β 的细胞外水平在暴露于 Cu-NPs 后均显著升高。作为 rBMEC 通透性增加的指标，P-表观比率对于 Cu-NPs（40 和 60nm）大约增加了两倍。
这些数据表明，Cu-NPs 可以在低浓度下诱导 rBMEC 增殖和/或在高浓度下诱导血脑屏障毒性和潜在的神经毒性。
