Title : Inhibition of mitochondrial RNA-driven inflammation by healthy plant-based bioactive compounds as a potential treatment approach
Abstract:
A wide range of medical conditions is associated with inflammation including autoimmune disease, cardiovascular disease, numerous cancers, diabetes, Alzheimer’s and many others. Consequently, inflammation contributes to high mortality rates and healthcare costs. We have studied inflammation in the context of oxidized mitochondrial RNA- and DNA-damage associated molecular patterns (DAMPs). These macromolecules trigger excessive immunostimulation through the induction of proinflammatory and type 1 interferon cytokines when released from the mitochondria to the cytoplasm. Given the highly detrimental effects of DAMPs and overall inflammation, we investigated the use of healthy plant-based phytochemicals including green tea EGCG, resveratrol, sulforaphane, quercetin, curcumin and olive oleuropein as potential treatments. Using an oxidized mitochondrial RNA (mitoxRNA) model with transfection into an interferon reporter THP-1 cell line, we observed a potent type I interferon induction following mitoxRNA transfection. This induction was strongly inhibited by pretreatment with the botanicals EGCG, resveratrol, sulforaphane and curcumin at low µM concentrations, with EGCG demonstrating especially potent inhibition. Subsequent RNAseq analyses revealed that EGCG pretreatment significantly inhibited the induction of many mitoxRNA-induced genes, especially immune-associated genes such as interferon stimulated genes (ISG). This suppression of immune genes was not a global EGCG effect. These studies identify potential healthy dietary options for minimizing mitochondrial RNA-mediated inflammation and associated disorders; provide insight to the mechanism of inflammation; and reveal a novel benefit of green tea EGCG for improving human health.
