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- W1676904719 abstract "Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly of industrialized nations, and there is increasing evidence to support a role for chronic inflammation in its pathogenesis. Mitochondrial DNA (mtDNA) has been recently reported to be pro-inflammatory in various diseases such as Alzheimer's and heart failure. Here, we report that intracellular mtDNA induces ARPE-19 cells to secrete inflammatory cytokines IL-6 and IL-8, which have been consistently associated with AMD onset and progression. The induction was dependent on the size of mtDNA, but not on specific sequence. Oxidative stress plays a major role in the development of AMD, and our findings indicate that mtDNA induces IL-6 and IL-8 more potently when oxidized. Cytokine induction was mediated by STING (Stimulator of Interferon Genes) and NF-κB as evidenced by abrogation of the cytokine response with the use of specific inhibitors (siRNA and BAY 11-7082, respectively). Finally, mtDNA primed the NLRP3 inflammasome. This study contributes to our understanding of the potential pro-inflammatory role of mtDNA in the pathogenesis of AMD." @default.
- W1676904719 created "2016-06-24" @default.
- W1676904719 creator A5012730403 @default.
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- W1676904719 creator A5050971382 @default.
- W1676904719 creator A5051931580 @default.
- W1676904719 creator A5069204345 @default.
- W1676904719 date "2015-11-01" @default.
- W1676904719 modified "2023-09-27" @default.
- W1676904719 title "Mitochondrial DNA has a pro-inflammatory role in AMD" @default.
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