Mitochondrial DNA has a pro-inflammatory role in AMD

作者：Dib, Bernard; Lin, Haijiang; Maidana, Daniel E.; Tian, Bo; Miller, John B.; Bouzika, Peggy; Miller, Joan W.; Vavvas, Demetrios G.^*

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2015, 1853(11): 2897-2906.

DOI：10.1016/j.bbamcr.2015.08.012

• Age-related macular degeneration
• Retinal pigment epithelium
• Mitochondrial DNA
• Inflammation
• NLRP3 inflammasome

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-kappa B 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.

• 出版日期2015-11