Manganese induces neuroinflammation via NF-κB/ROS NLRP3 pathway in rat brain striatum and HAPI cells

Backgrounds: Chronic exposure to excessive Mn can result in neurodegenerative symptoms, whose precise molecular mechanism remains largely unclear. Here, we measured the role and mechanism of NLRP3 in Mninduced neuroinflammation in vivo and vitro. Methods: The effects of Mn on NLRP3 activation were investigated by Westernblot, IHC, immunofluorescence analysis, as well as ELISA. We assessed NF-kappa B activation through measurement of phosphorylation and nuclear translocation. The mechanisms bywhich Mn induced NLRP3 activation were assessed by specific inhibitors. Results: We found that Mn exposure facilitated the activation of NLRP3 inflammasome to promote the production of IL-1 and IL-18 in dose- and time-dependent manners in HAPI cells. In addition, the NLRP3 inflammasome was also dramatically activated in microglia of rat brain striatum after Mn exposure. We also found increased ROS and NF-kappa B activation. Notably, the activation of NLRP3 was significantly attenuated by pretreatment with NF-kappa B and ROS inhibitors. Conclusion: These findings suggest that NLRP3 activation plays an important role in Mn-induced neuroinflammation, and it is associated with NF-kappa B and ROS.