Resveratrol Inhibits IgE-Mediated Basophilic Mast Cell Degranulation and Passive Cutaneous Anaphylaxis in Mice

Resveratrol is a phytoalexin abundantly found in red grape skin and is effective in antitumor and antiinflammation associated with immune responses. This study investigated whether resveratrol suppressed immunoglobulin (Ig)E-mediated allergic responses and passive cutaneous anaphylaxis (PCA) in rat RBL-2H3 mast cells and in BALB/c mice. The release of beta-hexosaminidase and histamine was enhanced in mast cells sensitized with anti-dinitrophenyl (DNP)-IgE and subsequently stimulated by DNP-human serum albumin (HSA), indicative of mast cell degranulation. When mast cells were pretreated with nontoxic resveratrol at 1-25 mu mol/L, such induction was dose dependently diminished. Spleen tyrosine kinase (Syk) and phospholipase C gamma (PLC gamma) of sensitized mast cells were activated by stimulation with DNP-HSA antigen, which was dampened by >= 5 mu mol/L resveratrol. The phosphorylation of protein kinase C (PKC)mu, and PKC theta was attenuated by administering resveratrol to DNP-HSA exposed mast cells, whereas quiescent PKC zeta/lambda. in sensitized cells was dose-dependently activated by resveratrol. Male BALB/c mice were sensitized for 24 h with DNP-IgE and orally administered with resveratrol 1 h before the DNP-HSA challenge. The histamine concentration was enhanced in sensitized mice challenged to DNP-HSA, which was reversed by administration of 10 mg/kg resveratrol. Additionally, it encumbered the tissue activation of Syk, PLC gamma, and PKC mu, in antigen-exposed mice. Resveratrol decreased IgE-mediated PCA and alleviated allergic edema of mouse ear and dorsal skin. Mast cell degranulation and allergic inflammation, accompanying the induction of monocyte chemotactic protein-1 and macrophage inflammatory protein-2, were inhibited by supplementing resveratrol to antigen-challenged mice. Resveratrol inhibited mast cell-derived, immediate-type allergic reactions, and these responses of resveratrol suggest possible therapeutic strategies in preventing allergic inflammatory diseases. J. Nutr. 143: 632-639, 2013.