Devon Shirley1, Cody McHale2, Gregorio Gomez3. 1. Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA. Electronic address: devon.shirley@uscmed.sc.edu. 2. Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA. Electronic address: mchalecc@email.sc.edu. 3. Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA. Electronic address: gregorio.gomez@uscmed.sc.edu.
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. GENERAL SIGNIFICANCE: 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.
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. GENERAL SIGNIFICANCE: 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: Sandra Odom; Gregorio Gomez; Martina Kovarova; Yasuko Furumoto; John J Ryan; Harry V Wright; Claudia Gonzalez-Espinosa; Margaret L Hibbs; Kenneth W Harder; Juan Rivera Journal: J Exp Med Date: 2004-06-01 Impact factor: 14.307