Effects of cis-resveratrol on inflammatory murine macrophages:: antioxidant activity and down-regulation of inflammatory genes

This study investigated for the first time the effects of the cis isomer of resveratrol (c-RESV) on the responses of inflammatory murine peritoneal macrophages, namely on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during the respiratory burst; on the biosynthesis of other mediators of inflammation such prostaglandins; and on the expression of inflammatory genes such as inducible nitric oxide synthase (NOS)-2 and inducible cyclooxygenase (COX)-2. Treatment with 1-100 muM c-RESV significantly inhibited intracellular and extracellular ROS production, and c-RESV at 10-100 muM significantly reduced RNS production. c-RESV at 1-100 muM was ineffective for scavenging superoxide radicals (O-2(.-)), generated enzymatically by a hypoxanthine (HX)/xanthine oxidase (XO) system and/or for inhibiting XO activity. However, c-RESV at 10-100 muM decreased nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase activity in macrophage homogenates. c-RESV at 100 muM decreased NOS-2 and COX-2 mRNA levels in lipopolysaccharide (LPS) interferon gamma (IFN-gamma)-treated macrophages. At 10-100 muM, c-RESV also significantly inhibited NOS-2 and COX-2 protein synthesis and decreased prostaglandin E-2 (PGE(2)) production. These results indicate that c-RESV at micromolar concentrations significantly attenuates several components of the macrophage response to proinflammatory stimuli (notably, production of O-2(.-) and of the proinflammatory mediators NO. and PGE(2)).