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: Seon-Young Han, Ji-Young Bae, Sin-Hye Park, Yun-Ho Kim, Jung Han Yoon Park, Young-Hee Kang
• Journal: The Journal of nutrition (J Nutr) Vol. 143 Issue 5 Pg. 632-9 (May 2013) ISSN: 1541-6100 [Electronic] United States
• PMID: 23514766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD24 Antigen
• Cd24a protein, mouse
• Chemokine CCL2
• Chemokine CXCL2
• Dinitrophenols
• Intracellular Signaling Peptides and Proteins
• Plant Extracts
• Serum Albumin
• Stilbenes
• dinitrophenyl-human serum albumin conjugate
• Immunoglobulin E
• Histamine
• Protein-Tyrosine Kinases
• SYK protein, human
• Syk Kinase
• Syk protein, mouse
• Syk protein, rat
• Phospholipase C gamma
• beta-N-Acetylhexosaminidases
• Resveratrol

Topics

• Anaphylaxis (immunology, metabolism, prevention & control)
• Animals
• Basophils
• CD24 Antigen (metabolism)
• Chemokine CCL2 (metabolism)
• Chemokine CXCL2 (metabolism)
• Dietary Supplements
• Dinitrophenols
• Dose-Response Relationship, Drug
• Edema (immunology, prevention & control)
• Histamine (metabolism)
• Histamine Release (drug effects)
• Immunoglobulin E (metabolism)
• Inflammation (prevention & control)
• Intracellular Signaling Peptides and Proteins (metabolism)
• Male
• Mast Cells (drug effects, metabolism)
• Mice
• Mice, Inbred BALB C
• Passive Cutaneous Anaphylaxis
• Phospholipase C gamma (metabolism)
• Phosphorylation
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)
• Protein-Tyrosine Kinases (metabolism)
• Rats
• Resveratrol
• Serum Albumin
• Skin (drug effects, immunology, metabolism)
• Stilbenes (pharmacology, therapeutic use)
• Syk Kinase
• Vitis (chemistry)
• beta-N-Acetylhexosaminidases (metabolism)