School of Basic Medical Sciences and Forensic Medicine, Baotou Medical College, Baotou, 014040, Inner Mongolia, China.
Institute of Neuroscience, Baotou Medical College, Baotou, 014040, Inner Mongolia, China.
Environ Sci Pollut Res Int. 2024 Mar;31(13):19844-19855. doi: 10.1007/s11356-024-32443-6. Epub 2024 Feb 17.
It is widespread of endemic fluorosis in China, and the exposure of excessive fluoride will cause nervous system disease and activate microglia. However, the mechanism of the damage is not clear. It is well-known that NLRP3/Caspase-1/GSDMD pathway, a classic pyroptosis pathway, is widely involved in the occurrence and development of nervous system-related diseases, infectious diseases, and atherosclerotic diseases. This research aimed to explore the molecular mechanism of sodium fluoride on inflammation and pyroptosis in BV2 microglia based on the NLRP3/Caspase-1/GSDMD signaling pathway. BV2 microglia was treated with sodium fluoride at the dose of 0.25, 1, and 2 mmol/L for 24, 48, and 72 h, respectively. Cell viability, cell morphology, lactate dehydrogenase content, and related proteins and genes were examined to investigate if sodium fluoride caused damage to BV2 microglia through the pyroptosis pathway. Dithiolam (5 μmol/L), a pyroptosis inhibitor, was added for further verification. NaF could induced BV2 cells injury in a dose-dependent fashion through disrupting the integrity of cell membranes and increasing IL-1β via upregulating NLRP3, Caspase-1, and its downstream protein GSDMD. Disulfiram could improve these changes caused by NaF. In conclusion, our results suggested that NLRP3/Caspase-1/GSDMD-mediated classical pyroptosis pathway was involved in fluoride-induced BV2 microglia damage.
中国存在广泛的地方性氟中毒，过量氟暴露会引起神经系统疾病并激活小胶质细胞。然而，其损伤机制尚不清楚。众所周知，NLRP3/Caspase-1/GSDMD 通路是一种经典的细胞焦亡通路，广泛参与神经系统相关疾病、感染性疾病和动脉粥样硬化性疾病的发生发展。本研究旨在探讨基于 NLRP3/Caspase-1/GSDMD 信号通路的氟化钠对 BV2 小胶质细胞炎症和细胞焦亡的分子机制。用不同浓度（0.25、1、2 mmol/L）的氟化钠分别处理 BV2 小胶质细胞 24、48 和 72 h，检测细胞活力、细胞形态、乳酸脱氢酶含量以及相关蛋白和基因，探讨氟化钠是否通过细胞焦亡通路对 BV2 小胶质细胞造成损伤。加入细胞焦亡抑制剂二硫代氨基甲酸（5 μmol/L）进行进一步验证。结果表明，氟化钠可通过破坏细胞膜的完整性和增加 IL-1β来诱导 BV2 细胞损伤，且呈剂量依赖性，这一过程与 NLRP3、Caspase-1 及其下游蛋白 GSDMD 的上调有关。二硫代氨基甲酸可改善氟化钠引起的这些变化。综上所述，本研究结果提示 NLRP3/Caspase-1/GSDMD 介导的经典细胞焦亡通路参与了氟化物诱导的 BV2 小胶质细胞损伤。
