The grape component resveratrol interferes with the function of chemoattractant receptors on phagocytic leukocytes

Resveratrol (3,5,4'-trihydroxystilbene) (RV) is a constituent of grape seeds with anti-inflammatory and anti-oxidant activities. In this study, we examined the capacity of RV to modulate the function of G protein-coupled chemoattractant receptors, which play important roles in inflammation and immune responses. RV, over a non-cytotoxic concentration range, inhibited chemotactic and calcium mobilization responses of phagocytic cells to selected chemoattractants. At low micromolar concentrations, RV potently reduced superoxide anion production by phagocytic leukocytes in response to the bacterial chemotactic peptide fMLF, a high affinity ligand for formylpeptide receptor FPR, and A beta42, an Alzheimer's disease-associated peptide and a ligand for the FPR variant FPRL1. In addition, RV reduced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and the activation of nuclear factor NF-kappaB induced by formylpeptide receptor agonists. These results suggest that the inhibition of the function of chemoattractant receptors may contribute to the anti-inflammatory properties of RV. Thus, RV may be therapeutically promising for diseases in which activation of formylpeptide receptors contributes to the pathogenic processes.