Manganese activates NLRP3 inflammasome signaling and propagates exosomal release of ASC in microglial cells.

ABSTRACT: Chronic, sustained inflammation underlies many pathological conditions, including neurodegenerative diseases. Divalent manganese (Mn2+) exposure can stimulate neurotoxicity by increasing inflammation. In this study, we examined whether Mn2+ activates the multiprotein NLRP3 inflammasome complex to promote neuroinflammation. Exposing activated mouse microglial cells to Mn2+ substantially augmented NLRP3 abundance, caspase-1 cleavage, and maturation of the inflammatory cytokine interleukin-1β (IL-1β). Exposure of mice to Mn2+ had similar effects in brain microglial cells. Furthermore, Mn2+ impaired mitochondrial ATP generation, basal respiratory rate, and spare capacity in microglial cells. These data suggest that Mn-induced mitochondrial defects drove the inflammasome signal amplification. W

SUBMITTER: Sarkar S 

PROVIDER: S-EPMC6420319 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature