白藜芦醇优先抑制IgE依赖性前列腺素D2的生物合成，但增强人皮肤肥大细胞的肿瘤坏死因子生成。
Resveratrol preferentially inhibits IgE-dependent PGD2 biosynthesis but enhances TNF production from human skin mast cells.
作者信息
Shirley Devon, McHale Cody, Gomez Gregorio
机构信息
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
出版信息
Biochim Biophys Acta. 2016 Apr;1860(4):678-85. doi: 10.1016/j.bbagen.2016.01.006. Epub 2016 Jan 14.
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.
背景
白藜芦醇是一种存在于红葡萄皮中的天然多酚，据报道具有抗炎特性，包括对衰老的保护作用。因此，白藜芦醇是一种常见的营养补充剂，也是非处方乳液和面霜中作为抗衰老产品销售的添加剂。对小鼠和小鼠骨髓来源的肥大细胞（BMMCs）的研究表明白藜芦醇具有抗过敏作用。然而，白藜芦醇对人原代肥大细胞的作用尚未见报道。
方法
从不同供体的正常皮肤组织中分离并纯化人肥大细胞。使用各种免疫测定、蛋白质印迹和定量实时PCR确定白藜芦醇对IgE依赖性过敏炎症介质释放的影响。
结果
低浓度（≤10 μM）的白藜芦醇抑制PGD2的生物合成，但不抑制脱颗粒。因此，COX-2表达受到抑制，但Syk、Akt、p38和p42/44（ERK）的磷酸化保持完整。令人惊讶的是，白藜芦醇显著增强了TNF的产生。在高浓度（100 μM）时，白藜芦醇显著抑制了除Syk磷酸化外分析的所有参数。
结论
在此，我们表明低浓度的白藜芦醇通过优先作用于花生四烯酸途径发挥其抗炎特性。我们还证明了白藜芦醇一种以前未被认识的促炎作用——在IgE依赖性激活后人成熟肥大细胞TNF产生的增强。
一般意义
这些发现表明，白藜芦醇作为一种治疗剂可以抑制PGD2介导的炎症，但对组胺介导的过敏反应无效。然而，白藜芦醇可能通过增强人皮肤肥大细胞中IgE依赖性TNF的产生而加剧或促进过敏性炎症。
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