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 high a 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.

Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes

“…Although several studies suggest the protective effect of resveratrol against allergic responses 22–27 , the precise role of Sirt1 in FcεRI-mediated mast cell activation has not been firmly established. In this study, we have shown that resveratrol blunts FcεRI signaling partly through the activation of Sirt1, which is linked to the LKB1/AMPK pathway.…”

The Role of the Mast Cell in Skin Aging

“…Resveratrol was confirmed to protect skin against photo damage through enhancing skin moisture and elasticity, reducing depth and length of wrinkles and decreasing intensity of spots [49][50][51]. In vitro test revealed that resveratrol directly inhibited degranulation of RBL-2H3 mast cells and human skin mast cells [52,53]. Resveratrol was reported to decrease the phosphorylation of ERK 1/2 in activated human mast cell-1(HMC-1) cells and inhibit NF-κB activation, which in turn lead to suppressed expression of TNF-α, IL-6, IL-8 and cyclooxygenase (COX)-2 [54].…”

Inflammatory Responses in Oro-Maxillofacial Region Expanded Using Anisotropic Hydrogel Tissue Expander

“…Notably, the presence of both IL-1α and TNF-α is a strong indication of inflammation. Moreover, TNF-α in the skin is produced mainly by activation of resident dermal mast cells [ 29 ]. Those cells contain numerous sizable active TNF-α inside their granules, which can be rapidly released to the extracellular space upon degradation of the cells.…”