Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages
Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages
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DOI：
10.1016/s0006-2952(99)00002-7
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发表时间：
1999-04-15
影响因子：
5.8
通讯作者：
Koop, DR
中科院分区：
文献类型：
--
作者：
Wadsworth, TL;Koop, DR
适量饮用红酒的有益作用部分归因于其抗氧化成分的存在。氧化应激是NF（核因子）- κ B/Rel转录因子家族的激活刺激物，其结合位点位于许多参与炎症和免疫反应的基因的启动子区域。在巨噬细胞系RAW 264.7中测定了脂多糖（LPS）刺激nf - κ B活化及随后肿瘤坏死因子α (tnf - α)和NO产生的影响。出乎意料的是，葡萄酒多酚类物质槲皮素和白藜芦醇以及抗氧化剂n -乙酰半胱氨酸（NAC）并没有抑制lps诱导的nf - κ B复合物p50/65的激活，这是由迁移率变化确定的。槲皮素抑制lps诱导的p50/50。Northern blot分析表明，槲皮素（0.1和0.2 mM）抑制LPS依赖性诱导型一氧化氮合酶（iNOS） mRNA的产生，减少NO的释放。通过ELISA检测，黄酮类化合物对lps诱导的tnf - α mRNA无影响，但可降低lps刺激的tnf - α释放。白藜芦醇（0.05和0.1 mM）转录后降低lps诱导的亚硝酸盐释放。它增加了tnf - α mRNA和蛋白的基础水平，增强了LPS诱导的tnf - α mRNA和细胞因子的释放。我们的研究结果不支持葡萄酒抗氧化剂抑制LPS诱导的NF-kappa B激活的观点，相反，它们对LPS激活的基因有更多的选择性作用。生物化学杂志57；8:941 - 949, 1999。(C) 1999 Elsevier Science Inc.；
The beneficial effects of moderate red wine consumption have been attributed, in part, to the presence of antioxidant components. Oxidant stress is an activating stimulus for the NF (nuclear factor)-kappa B/Rel family of transcription factors, which have binding sites in the promoter regions of many genes involved in inflammatory and immune responses. The effect of lipopolysaccharide (LPS) stimulated activation of NF-kappa B and the subsequent production of tumor necrosis factor alpha (TNF-alpha) and NO was determined in the macrophage cell line RAW 264.7. Unexpectedly, the wine polyphenolics quercetin and resveratrol and the antioxidane N-acetylcysteine (NAC) did not inhibit LPS-induced activation of the NF-kappa B complex p50/65, as determined by mobility shift. Quercetin inhibited LPS-induced p50/50. Northern blot analysis indicated that quercetin (0.1 and 0.2 mM) inhibited LPS dependent production of inducible nitric oxide synthase (iNOS) mRNA and decreased NO release, as measured by the Griess reaction. This flavonoid had no effect on LPS-induced TNF-alpha mRNA, but decreased LPS-stimulated TNF-alpha release, as measured by ELISA. Resveratrol (0.05 and 0.1 mM) posttranscriptionally decreased LPS-induced nitrite release. It increased basal levels of TNF-alpha mRNA and protein and enhanced LPS induced TNF-alpha mRNA and cytokine release. Our results do not support the view that wine antioxidants inhibit: LPS-induced NF-kappa B activation but instead that they have a more selective action on genes activated by LPS. BIOCHEM PHARMACOL 57;8:941-949, 1999. (C) 1999 Elsevier Science Inc.