CdTe and CdTe@ZnS quantum dots induce IL-β-mediated inflammation and pyroptosis in microglia
CdTe and CdTe@ZnS quantum dots induce IL-β-mediated inflammation and pyroptosis in microglia
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CdTe 和 CdTe@ZnS 量子点诱导小胶质细胞中 IL-1 介导的炎症和细胞焦亡
DOI：
10.1016/j.tiv.2020.104827
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发表时间：
2020-06-01
影响因子：
3.2
通讯作者：
Tang, Meng
中科院分区：
文献类型：
--
作者：
Liang, Xue;Wu, Tianshu;Tang, Meng
由于比非镉量子点更优越的光学性能和荧光效率，CdTe量子点仍然被广泛认为是优秀的荧光探针。因此，找到控制其毒性的方法是很重要的。在本研究中，Cd Te量子点和Cd Te@ZnS量子点均可引起BV2细胞IL-1β介导的炎症反应，并伴有下垂，但其毒性作用弱于Cd Te量子点，说明其具有一定的保护作用。在探讨量子点引起炎症损伤的分子机制时，研究结果表明，含镉量子点暴露激活了参与NLRP3炎症体启动和前IL-1β表达的核因子-kappaB。在此之后，量子点诱导的过量ROS的产生触发了NLRP3炎症体的激活，导致活化的caspase-1将前-IL-1β处理为成熟的IL-1β释放和炎性细胞死亡，即下垂。幸运的是，抑制caspase-1、NF-kappa B和ROS或下调NLRP3都能有效地减轻量子点引起的BV2细胞IL-1β分泌增加和细胞死亡。本研究提供了两种方法来减轻含镉量子点的毒性，一种是用壳层包裹裸核量子点，另一种是抑制其毒性途径。由于后一种方法比前一种方法更有效，因此通过基于机制的风险评估来评估量子点以识别可控的毒性靶标具有重要意义。
CdTe quantum dots (QDs) are still widely considered as excellent fluorescent probes because of their far more superior optical performance and fluorescence efficiency than non-cadmium QDs. Thus, it is important to find ways to control their toxicity. In this study, CdTe QDs and CdTe@ZnS QDs both could cause IL-1 beta-mediated inflammation following with pyroptosis in BV2 cells, but the toxic effects caused by CdTe@ZnS QDs was weaker than CdTe QDs, which demonstrated the partial protection of ZnS shell. When investigating the molecular mechanisms of QDs causing the inflammatory injury, the findings suggested that cadmium-containing QDs exposure activated NF-kappa B that participated in the NLRP3 inflammasome priming and pro-IL-1 beta expression. After that, QDs-induced excessive ROS generation triggered the NLRP3 inflammasome activation and resulted in active caspase-1 to process pro-IL-1 beta into mature IL-1 beta release and inflammatory cell death, i.e. pyroptosis. Fortunately, the inhibitions of caspase-1, NF-kappa B and ROS or knocking down of NLRP3 all effectively attenuated the increases in the IL-1 beta secretion and cell death caused by QDs in BV2 cells. This study provided two methods to alleviate the toxicity of cadmium-containing QDs, in which one is to encapsulate bare-core QDs with a shell and the other is to inhibit their toxic pathways. Since the latter way is more effective than the former one, it is significant to evaluate QDs through a mechanism-based risk assessment to identify controllable toxic targets.