title: Resveratrol inhibits IgE-mediated basophilic mast cell degranulation and passive cutaneous anaphylaxis in mice.
abstract: 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 β-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 μmol/L, such induction was dose dependently diminished. Spleen tyrosine kinase (Syk) and phospholipase Cγ (PLCγ) of sensitized mast cells were activated by stimulation with DNP-HSA antigen, which was dampened by ≥5 μmol/L resveratrol. The phosphorylation of protein kinase C (PKC)μ and PKCθ was attenuated by administering resveratrol to DNP-HSA-exposed mast cells, whereas quiescent PKCζ/λ 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, PLCγ, and PKCμ 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.
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon, Korea.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Han
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Bae
authors.forename: Sin-Hye
authors.initials: SH
authors.lastname: Park
authors.forename: Yun-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kang
mesh_terms: D000707:Anaphylaxis / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D001491:Basophils; D051927:CD24 Antigen / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D019587:Dietary Supplements; D004140:Dinitrophenols; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000276:immunology / Q000517:prevention & control; D006632:Histamine / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects*; D007073:Immunoglobulin E / Q000378:metabolism*; D007249:Inflammation / Q000517:prevention & control; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010323:Passive Cutaneous Anaphylaxis; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D000077185:Resveratrol; D012709:Serum Albumin; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D000072377:Syk Kinase; D027843:Vitis / Q000737:chemistry; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D004140:Dinitrophenols; D047908:Intracellular Signaling Peptides and Proteins; D010936:Plant Extracts; D012709:Serum Albumin; D013267:Stilbenes; C058064:dinitrophenyl-human serum albumin conjugate; D007073:Immunoglobulin E; D006632:Histamine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C000606898:Syk protein, rat; D051966:Phospholipase C gamma; D001619:beta-N-Acetylhexosaminidases; D000077185:Resveratrol