Inhibitory effects of resveratrol on human mast cell degranulation, cytokine, chemokine and leukotriene release

Abstract

Resveratrol, a polyphenol abundant in peanuts, red wine and the skin of grapes, has been shown to have anti-cancer, anti-oxidant and anti-inflam- matory activities, and may also have beneficial effects on allergic inflammation. We investigated the effects of resveratrol on human mast cell ac- tivation in comparison to the anti-allergy drug tranilast. In LAD2 mast cells, both resveratrol and tranilast inhibited degranulation induced by the mast cell activators substance P, IgE/anti-IgE, and compound 48/80. Resveratrol inhibition was immediate, preventing degranulation when add- ed simultaneously to physiological stimuli, and the effect was sustained for up to 24 hrs. The inhibitory effect was not cAMP dependent, but may be attributable to calcium modulation, as resveratrol, and to a lesser extent tranilast, pre- vented substance P-induced increases in intra- cellular calcium. Resveratrol attenuated sub-stance P-induced TNF and MCP-1 production and inhibited IgE-mediated release of cysteinyl leukotrienes, whereas tranilast was ineffective. Furthermore, both resveratrol and tranilast re-duced expression of the high affinity IgE recep-tor, FcεRI, on LAD2 cells. The effects of resvera- trol on mast cell activation were more marked in human primary CD34+-derived mast cells (HuMC), and the polyphenol was significantly more effi- cacious than tranilast in these cells. In conclu- sion, resveratrol inhibited key aspects of human mast cell activation to physiological stimuli, and was comparable, if not more efficacious than the anti-allergy drug tranilast. Thus, resveratrol may be an effective therapeutic agent for the treat-ment of allergic disease.