Resveratrol attenuates monocyte-to-macrophage differentiation and associated inflammation via modulation of intracellular GSH homeostasis: Relevance in atherosclerosis.

摘要: Monocyte-to-macrophage differentiation promotes an inflammatory environment within the arterial vessel wall that causes a mal-adaptive immune response, which contributes to progression of atheromatous plaque formation. In current study, we show resveratrol, well-known antioxidant, dose-dependently attenuated phorbol myristate acetate (PMA)-induced monocyte-to-macrophage differentiation, as measured by cell adhesion, increase in size, and scavenger receptor expression THP-1 monocytes. Also, resveratrol significantly inhibited PMA-induced pro-inflammatory cytokine/chemokine matrix metalloprotease (MMP-9) production. This inhibitory effect on monocyte results from its ability restore intracellular glutathione (GSH) status, presence buthionine sulfoximine (BSO) failed affect differentiation. Furthermore, inflammation was greatly when cells were co-treated with N-Acetyl-l-cysteine (NAC), GSH precursor, while BSO aggravated these processes. These also mediated up-regulation is due AMP-activated protein kinase (AMPK)-α activation, compound C (AMPK inhibitor) treatment drastically depleted exacerbated cytokine More importantly, chronic administration efficiently prevented infiltration markedly diminished angiotensin (Ang)-II-induced formation apolipoprotein-E knockout (ApoE(-/-)) mice. We conclude that, status plays critical role regulating restoring levels, inhibits Taken together, suggest can attenuate atherosclerosis, at least, part, inhibiting cytokines