Indirect effects of TiO2 nanoparticle on neuron-glial cell interactions
Indirect effects of TiO2 nanoparticle on neuron-glial cell interactions
复制标题
DOI：
10.1016/j.cbi.2016.05.024
复制
发表时间：
2016-07-25
影响因子：
5.1
通讯作者：
Huang, Yuh-Jeen
中科院分区：
文献类型：
--
作者：
Hsiao, I-Lun;Chang, Chia-Cheng;Huang, Yuh-Jeen
虽然二氧化钛纳米颗粒（TiO（2）NPs）是消费品中常用的纳米材料，但对其有害影响，特别是对中枢神经系统的影响知之甚少。为了研究这个问题，将ALT星形胶质细胞样、BV-2小胶质细胞和分化的N2 a神经母细胞瘤细胞暴露于6 nm的100%TiO2纳米颗粒。在NP处理之前预处理脂多糖（LPS）以激活神经胶质细胞，以模拟脑损伤下的NP暴露。我们发现ALT和BV-2细胞比N2 a细胞摄取更多的NP，导致细胞活力降低。TiO（2）NPs在三种细胞系中诱导IL-1 β，在N2 a中诱导IL-6。LPS激活的BV-2比正常BV-2吸收更多的TiO（2）NPs，并且比激活的BV-2释放更多的细胞内/细胞外活性氧（ROS）、IL-1 β、IL-6和MCP-1。ALT中网格蛋白和小窝依赖的内吞作用和BV-2中网格蛋白依赖的内吞作用和吞噬作用的参与都具有缓慢的NP向溶酶体的移位速率，这可能导致缓慢的ROS产生（24 h后）。虽然TiO（2）NPs没有直接导致N2 a活力丧失，但通过将NP间接暴露于Transwell系统中LPS活化的BV-2的底部腔室，由于BV-2释放H2 O2和/或TNF-α，TiO（2）NPs在上部N2 a腔室中引起晚期凋亡和细胞活力丧失。然而，当TiO（2）NPs暴露于ALT-N2 a或ALT-BV-2共培养物时，未观察到N2 a或BV-2细胞的不良反应。这些结果表明，神经元损伤可能是由于TiO 2 NP介导的ROS和/或细胞因子从小胶质细胞释放，而不是从星形胶质细胞释放。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Although, titanium dioxide nanoparticles (TiO(2)NPs) are nanomaterials commonly used in consumer products, little is known about their hazardous effects, especially on central nervous systems. To examine this issue, ALT astrocyte-like, BV-2 microglia and differentiated N2a neuroblastoma cells were exposed to 6 nm of 100% anatase TiO(2)NPs. A lipopolysaccharide (LPS) was pre-treated to activate glial cells before NP treatment for mimicking NP exposure under brain injury. We found that ALT and BV-2 cells took up more NPs than N2a cells and caused lower cell viability. TiO(2)NPs induced IL-1 beta in the three cell lines and IL-6 in N2a. LPS-activated BV-2 took up more TiO(2)NPs than normal BV-2 and released more intra/extracellular reactive oxygen species (ROS), IL-1 beta, IL-6 and MCP-1 than did activated BV-2. Involvement of clathrin- and caveolae-dependent endocytosis in ALT and clathrin-dependent endocytosis and phagocytosis in BV-2 both had a slow NP translocation rate to lysosome, which may cause slow ROS production (after 24 h). Although TiO(2)NPs did not directly cause N2a viability loss, by indirect NP exposure to the bottom chamber of LPS-activated BV-2 in the Transwell system, they caused late apoptosis and loss of cell viability in the upper N2a chamber due to H2O2 and/or TNF-alpha release from BV-2. However, none of the adverse effects in N2a or BV-2 cells was observed when TiO(2)NPs were exposed to ALT-N2a or ALT-BV-2 co-culture. These results demonstrate that neuron damage can result from TiO2NP-mediated ROS and/or cytokines release from microglia, but not from astrocytes. (C) 2016 Elsevier Ireland Ltd. All rights reserved.