Effects of resveratrol, piceatannol, triacetoxystilbene, and genistein on the inflammatory response of human peripheral blood leukocytes
Effects of resveratrol, piceatannol, triacetoxystilbene, and genistein on the inflammatory response of human peripheral blood leukocytes
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DOI：
10.1002/mnfr.200400099
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发表时间：
2005-05-01
影响因子：
5.2
通讯作者：
Schwager, J
中科院分区：
文献类型：
--
作者：
Richard, N;Porath, D;Schwager, J
炎症过程与疾病的病因学有关。我们分析了白藜芦醇、白藜芦醇、人工合成三乙酰氧基二苯乙烯(TAS)和金雀异黄素(Bonistein(TM))对炎症介质包括前列腺素E-2(PGE(2))、肿瘤坏死因子-α(TNF-α)、白介素和趋化因子的产生的影响，这些介质参与了炎症的发展。为诱导炎症反应，用脂多糖(LPS)和干扰素-γ(干扰素-γ)刺激人外周血单核和/或中性粒细胞，测定其产生前列腺素E(2)、白介素8(IL-8)和肿瘤坏死因子-α(TNF-α)。作为对刺激的响应，基因在2小时内基本上被激活(例如，TNF-α、IL-1α)，或在较晚的阶段(例如，COX-2、IL-6、IL-8)被激活。与染料木素不同，白藜芦醇和相关化合物呈剂量依赖性地减少PGE(2)的产生。金雀异黄素、匹卡坦醇和TAS可减少肿瘤坏死因子-α和白介素8的分泌。TAS降低COX-2、TNF-α、IL-8、IL-6和IL-1α的mRNA水平，而白藜芦醇则抑制IL-8和TNF-α的早期表达。Piceatanyl的表现优于白藜芦醇，但没有与TAS相匹配的效果。金雀异黄素可下调肿瘤坏死因子-α和白介素8的表达。这些物质改变了内毒素/干扰素-γ诱导的单核细胞基因表达，而不是多形核白细胞基因表达。免疫印迹分析证实了白藜芦醇和染料木素的不同活性模式。总而言之，白藜芦醇及其衍生物在不同程度上减轻了外周血淋巴细胞的炎症反应，而金雀异黄素则作用于细胞因子和促炎因子。
Inflammatory processes are involved in the etiology of diseases. We analyzed the effect of resveratrol, piceatannol, synthetic tri-acetoxystilbene (TAS), and genistein (Bonistein (TM)) on the production of inflammatory mediators including prostaglandin E-2 (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), interleukins, and chemokines, which participate in the progression of inflammation. In order to induce inflammatory responses, human peripheral blood mononuclear and/or polymorphonuclear leukocytes were stimulated with lipopolysaccharide (LPS) and interferon-gamma (IFN gamma) and the production of PGE(2), interleukin-8 (IL-8), and TNF-alpha was determined. In response to the stimuli, genes were substantially activated within < 2 h (e. g., TNF-alpha, IL-1 alpha), or at a later stage, (e. g., COX-2, IL-6, IL-8). Unlike genistein, resveratrol and related compounds dose-dependently reduced PGE(2) production. Genistein, piceatannol, and TAS diminished secretion of TNF-a, and IL-8. TAS reduced mRNA levels of COX-2, TNF-alpha, IL-8, IL-6, and IL-1 alpha, while resveratrol impaired early expression of IL-8 and TNF-alpha. Piceatannol out-performed resveratrol, yet without matching TAS. Genistein downregulated TNF-a and IL-8 expression. These substances altered the LPS/IFN gamma-induced gene expression in mononuclear cells rather than in polymorphonuclear leukocytes. Immunoblot analyses corroborated the distinct activity pattern of resveratrol and genistein. In conclusion, resveratrol and their derivatives attenuated the inflammatory response of PBLs at several levels, whereas genistein acts on cytokines and proinflammatory interleukins.