@article {541271,
	title = {Mitochondrial DNA has a pro-inflammatory role in AMD.},
	journal = {Biochim Biophys Acta},
	volume = {1853},
	number = {11 Pt A},
	year = {2015},
	month = {2015 Nov},
	pages = {2897-906},
	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{\textquoteright}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.},
	issn = {0006-3002},
	doi = {10.1016/j.bbamcr.2015.08.012},
	author = {Dib, Bernard and Lin, Haijiang and Maidana, Daniel E and Tian, Bo and Miller, John B and Bouzika, Peggy and Miller, Joan W and Vavvas, Demetrios G}
}
