Fluoride promotes the secretion of inflammatory factors in microglia through NLRP3/Caspase-1/GSDMD pathway.

Abstract

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 2mmol/L for 24, 48, and 72h, 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 (5μmol/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 couldimprove 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.