Alpha-lipoic acid represses IL-1B and IL-6 through DNA methylation in ovarian cells

Alpha-lipoic acid (ALA) is an endogenous molecule with pleiotropic effects, including antioxidant and antiinflammatory activity mediated by NF-kB nuclear factor, that has the potential to regulate pro- and anti-inflammatory cytokines. ALA-induced downregulation of two major pro-inflammatory cytokines, IL-1B and IL-6, has been ascertained in different tissues and experimental models. In pregnant women, ALA-dependent modulation of inflammation is beneficial for the implantation and the management of threatened miscarriage and preterm delivery. Recent data indicate that IL-1B and IL-6 expression are modulated by DNA methylation; we previously demonstrated that hypomethylation of these two genes is associated to increased expression in human brain. We then investigated whether ALA-dependent IL-1B and IL-6 downregulation is mediated by epigenetic changes in ovarian experimental models, studying the DNA methylation profile of IL-1B and IL-6 5′-flanking regions in human ovarian epithelial cell lines. We found that ALA induce hypermethylation of IL-1B and IL-6 5′-flanking regions and is associated to IL-1B and IL-6 mRNA and protein downregulation. These data provide novel insights on the antiinflammatory effects of ALA and support its clinical use in pregnancy complications.