title: Inhibition of phagocytosis and lysosomal acidification suppresses neurotoxic prion peptide-induced NALP3 inflammasome activation in BV2 microglia.
abstract: Prion diseases are neurodegenerative disorders characterized by the accumulation of misfolded prion protein. In a previous study, we showed that neurotoxic prion peptide (PrP106-126) induced NALP3 inflammasome activation in mouse primary and immortalized microglia. In the present work, we examined the relevance of phagocytosis and lysosomal acidification to the activation of the NALP3 inflammasome in PrP106-126-stimulated microglia. Our results showed that the inhibition of phagocytosis or lysosomal acidification significantly reduced IL-1β and IL-18 production, downregulated NALP3 and ASC expression, and decreased the expression of proinflammatory factors. We concluded that phagocytosis and lysosomal acidification are necessary for PrP106-126-induced NALP3 activation in BV2 cells.
authors.affiliation: Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Fushan
authors.initials: F
authors.lastname: Shi
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kouadir
authors.forename: Yongyao
authors.initials: Y
authors.lastname: Fu
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yang
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yin
authors.forename: Deming
authors.initials: D
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002461:Cell Line, Transformed; D015638:Cytochalasin D / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D058847:Inflammasomes / Q000187:drug effects / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008247:Lysosomes / Q000276:immunology* / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D061251:Primary Cell Culture; D011328:Prions / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D018942:Macrolides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D019384:Nucleic Acid Synthesis Inhibitors; D010446:Peptide Fragments; D011328:Prions; C082161:lipopolysaccharide A; C082632:prion protein (106-126); D015638:Cytochalasin D; C040929:bafilomycin A1