Cellular & Molecular Immunology. 2004 Feb, Vol.1, No.1, pp.50-56.
The Grape Component Resveratrol Interferes with the Function of Chemoattractant Receptors on Phagocytic Leukocytes

Hengyi Tao^{1, 6}, Chunfu Wu⁴, Ye Zhou¹, Wanghua Gong³, Xia Zhang², Pablo Iribarren¹, Yuqing Zhao⁵, Yingying Le¹ and Jiming Wang^{1, 7
1}Laboratory of Molecular Immunoregulation, ²Laboratory of Experimental Immunology, Center for Cancer Research, and ³Basic Research Program, SAIC-Frederick Inc., National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
⁴Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.
⁵Research Center for Modernization of Chinese Materia Medica Liaoning Province, Shenyang 110000, China.
⁶Department of Nautical Medicine, Shanghai Changzheng Hospital, Shanghai, China.
⁷Corresponding Author: Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute Frederick, Building 560, Room 31-40, Frederick, Maryland 21702; 301-846-6979. Fax: 301-846-7042, E-mail: wangji@mail.ncifcrf.gov.

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 Aβ42, 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-κB 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.