RESVERATOL EPIGENETICALLY REGULATES INFLAMMATORY GENES IN MURINE BV2 MICROGLIA EXPOSED TO HYPOXIA

Abstract

Microglial cells are activated in response to hypoxic insults. Resveratrol, a polyphenol, was also found to inhibit microglial activation in different neuropathologies. However, the molecular and epigenetic mechanisms underlying this process remain unknown. This study was aimed at elucidating the mechanisms underlying the effect of resveratrol on microglial activation in hypoxic conditions. We observed that hypoxia upregulates pro-inflammatory cytokines (TNFα and iNOS) and downregulates anti-inflammatory gene IL-10 in microglia. Upon treatment of hypoxic microglia with resveratrol, there was an increase in the IL-10 gene expression when compared to untreated hypoxic microglia. In addition, we observed that there was a significant increase in the H3K27me3 mark in hypoxia exposed microglia which decreases upon treatment with resveratrol. Furthermore, there was a significant decrease in H3K27me3 mark at the IL-10 promoter in resveratrol-treated hypoxic microglia. In conclusion, resveratrol was found to epigenetically induce the expression of anti-inflammatory cytokine IL-10 in hypoxia-activated microglia.