title: Resveratrol preferentially inhibits IgE-dependent PGD2 biosynthesis but enhances TNF production from human skin mast cells.
abstract: BACKGROUND
  Resveratrol, a natural polyphenol found in the skin of red grapes, is reported to have anti-inflammatory properties including protective effects against aging. Consequently, Resveratrol is a common nutritional supplement and additive in non-prescription lotions and creams marketed as anti-aging products. Studies in mice and with mouse bone marrow-derived mast cells (BMMCs) have indicated anti-allergic effects of Resveratrol. However, the effects of Resveratrol on human primary mast cells have not been reported.
  
  
  METHODS
  Human mast cells were isolated and purified from normal skin tissue of different donors. The effect of Resveratrol on IgE-dependent release of allergic inflammatory mediators was determined using various immunoassays, Western blotting, and quantitative real-time PCR.
  
  
  RESULTS
  Resveratrol at low concentrations (≤10 μM) inhibited PGD2 biosynthesis but not degranulation. Accordingly, COX-2 expression was inhibited but phosphorylation of Syk, Akt, p38, and p42/44 (ERKs) remained intact. Surprisingly, TNF production was significantly enhanced with Resveratrol. At a high concentration (100 μM), Resveratrol significantly inhibited all parameters analyzed except Syk phosphorylation.
  
  
  CONCLUSIONS
  Here, we show that Resveratrol at low concentrations exerts its anti-inflammatory properties by preferentially targeting the arachidonic acid pathway. We also demonstrate a previously unrecognized pro-inflammatory effect of Resveratrol--the enhancement of TNF production from human mature mast cells following IgE-dependent activation.
  
  
  CONCLUSIONS
  These findings suggest that Resveratrol as a therapeutic agent could inhibit PGD2-mediated inflammation but would be ineffective against histamine-mediated allergic reactions. However, Resveratrol could potentially exacerbate or promote allergic inflammation by enhancing IgE-dependent TNF production from mast cells in human skin.
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA. Electronic address: devon.shirley@uscmed.sc.edu.
authors.forename: Devon
authors.initials: D
authors.lastname: Shirley
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA. Electronic address: mchalecc@email.sc.edu.
authors.forename: Cody
authors.initials: C
authors.lastname: McHale
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA. Electronic address: gregorio.gomez@uscmed.sc.edu.
authors.forename: Gregorio
authors.initials: G
authors.lastname: Gomez
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D015230:Prostaglandin D2 / Q000276:immunology*; D000077185:Resveratrol; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D013267:Stilbenes; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000077185:Resveratrol; D015230:Prostaglandin D2
keywords: Allergy; Inflammation; Mast cells; Prostaglandin D2; Resveratrol; Tumor necrosis factor