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 Aβ1-40 could 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 Aβ1-40 on 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.
Keywords:
NLRP3 inflammasome; age-related macular degeneration; amyloid β; reactive oxygen species.
© 2016 Wiley Periodicals, Inc.
MeSH terms
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Amyloid / metabolism
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Amyloid beta-Peptides / metabolism*
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Cell Line
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Enzyme Inhibitors / pharmacology
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Humans
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Inflammasomes / drug effects
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Inflammasomes / immunology
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Inflammasomes / metabolism*
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Kinetics
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Lipopolysaccharides / toxicity
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MAP Kinase Signaling System / drug effects
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Macular Degeneration / enzymology
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Macular Degeneration / immunology
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Macular Degeneration / metabolism*
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Mitochondria / drug effects
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Mitochondria / immunology
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Mitochondria / metabolism
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NADPH Oxidases / antagonists & inhibitors
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NADPH Oxidases / metabolism*
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NF-kappa B / agonists
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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NLR Family, Pyrin Domain-Containing 3 Protein / agonists*
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NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
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Oxidative Stress / drug effects
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Peptide Fragments / metabolism*
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Reactive Oxygen Species / agonists
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Reactive Oxygen Species / antagonists & inhibitors
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Reactive Oxygen Species / metabolism*
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Retinal Pigment Epithelium / drug effects
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Retinal Pigment Epithelium / immunology
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Retinal Pigment Epithelium / metabolism*
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Sulfones / pharmacology
Substances
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Amyloid
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Amyloid beta-Peptides
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Enzyme Inhibitors
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Inflammasomes
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Lipopolysaccharides
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NF-kappa B
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NLR Family, Pyrin Domain-Containing 3 Protein
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NLRP3 protein, human
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Peptide Fragments
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Reactive Oxygen Species
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Sulfones
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amyloid beta-protein (1-40)
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4-(2-aminoethyl)benzenesulfonylfluoride
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NADPH Oxidases