MPA-modified CdTe quantum dots increased interleukin-1beta secretion through MyD88-dependent Toll-like receptor pathway and NLRP3 inflammasome activation in microglia

作者：Wu, Tianshu; Liang, Xue; He, Keyu; Wei, Tingting; Wang, Yan; Lu, Jie; Yao, Ying; Zhang, Ting; Xue, Yuying; Tang, Meng^*

来源：Toxicology in Vitro, 2018, 52: 41-51.

DOI：10.1016/j.tiv.2018.05.014

• Quantum dot
• Toll-like receptor
• Interleukin-1beta
• Inflammasome
• Microglia

The excellent optical properties of CdTe quantum dots (QDs) make researchers realize their value on the application of biomedicine, especially neuroscience, as an advanced fluorescent probe. Thus, it is important to evaluate the biosafety of CdTe QDs on the central nervous system (CNS). Our previous studies have conducted a systematic biosafety evaluation of CdTe QDs on the CNS and found several toxic endpoints, one of which is the inflammation on the rat hippocampus, but their underlying mechanism remains unclear. In this study, when BV2 microglial cells were exposed to CdTe QDs with doses < 20 nM, there was no obviously adverse effect. However, 40 nM CdTe QDs exposure could significantly activate the BV2 cells and increase the pro-inflammatory cytokine IL-1 beta secretion. Molecular biology analyses suggested that both TLR2/MyD88/NF-kappa B pathway and NLRP3 inflammasome participated in the CdTe QD-induced IL-1 beta secretion. The former served as the first signal for pro-IL-1 beta expression, while the later played a role on the maturation of pro-IL-1 beta into IL-1 beta. The results, taken together, demonstrated that MPA-modified CdTe QDs exposure with a high concentration was capable of activating microglial cells and promoting IL-1 beta secretion, which was highly correlated with the activations of both TLR2/MyD88/NF-kappa B pathway and ROS-induced NLRP3 inflammasome. These findings provide some mechanistic insights regarding the neuroinflammatory responses to cadmium-based QDs.

• 出版日期2018-10
• 单位东南大学