title: Amyloid β induces NLRP3 inflammasome activation in retinal pigment epithelial cells via NADPH oxidase- and mitochondria-dependent ROS production.
abstract: Amyloid β (Aβ)-induced chronic inflammation is believed to be a key pathogenic process in early-stage age-related macular degeneration (AMD). Nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation triggered by Aβ is responsible for retinal pigment epithelium (RPE) dysfunction in the onset of AMD; however, the detailed molecular mechanism remains unclear. In this study, we investigated the involvement of NADPH oxidase- and mitochondria-derived reactive oxygen species (ROS) in the process of Aβ1-40-induced NLRP3 inflammasome activation in LPS-primed ARPE-19 cells. The results showed that Aβ1-40could induce excessive ROS generation, MAPK/NF-κB signaling activation and subsequently NLRP3 inflammasome activation in LPS-primed ARPE-19 cells. Furthermore, the inductive effect of Aβ1-40on NLRP3 inflammasome activation was mediated in a manner dependent on NADPH oxidase- and mitochondria-derived ROS. Our findings may provide a novel insight into the molecular mechanism by which Aβ contributes to the early-stage AMD.
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, Jiangsu Province, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, Jiangsu Province, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, Jiangsu Province, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, Jiangsu Province, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Faculty of Pharmacy, University of Sydney, NSW, 2006, Australia.
authors.forename: Fanfan
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Save Sight Institute, University of Sydney, NSW, 2000, Australia.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008268:Macular Degeneration / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000819:agonists* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D058847:Inflammasomes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D013450:Sulfones; C078592:amyloid beta-protein (1-40); C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D019255:NADPH Oxidases
keywords: NLRP3 inflammasome; age-related macular degeneration; amyloid β; reactive oxygen species