Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, 299 Viale Regina Elena, 00161 Rome, Italy.
Oxid Med Cell Longev. 2013;2013:574029. doi: 10.1155/2013/574029. Epub 2013 Jul 9.
Advanced glycation end products (AGEs), generated through nonenzymatic glycosylation of proteins, lipids, and nucleic acids, accumulate in the body by age thus being considered as biomarkers of senescence. Senescence is characterized by a breakdown of immunological self-tolerance, resulting in increased reactivity to self-antigens. Previous findings suggest that AGE and its receptor RAGE may be involved in the pathogenesis of autoimmune reactions through dendritic cell (DC) activation. The aim of this study was to investigate whether resveratrol, a polyphenolic antioxidant compound with tolerogenic effects on DCs, was able to counteract the mechanisms triggered by AGE/RAGE interaction on DCs. By immunochemical and cytofluorimetric assays, we demonstrated that in vitro pretreatment of human monocyte-derived DCs with resveratrol prevents DC activation in response to glucose-treated albumin (AGE-albumin). We found that resveratrol exerts an inhibitory effect on DC surface maturation marker and RAGE up-regulation in response to AGE-albumin. It also inhibited proinflammatory cytokine expression, allostimulatory ability upregulation, mitogen-activated protein (MAP) kinases, and NF-κB activation in AGE-albumin-stimulated DCs. We suggest that resveratrol, by dismantling AGE/RAGE signaling on DCs may prevent or reduce increased reactivity to self-molecules in aging.
糖基化终产物 (AGEs) 是蛋白质、脂质和核酸非酶糖基化的产物，随着年龄的增长在体内积累，因此被认为是衰老的生物标志物。衰老的特征是免疫自身耐受的破坏，导致对自身抗原的反应性增加。先前的研究结果表明，AGE 及其受体 RAGE 可能通过树突状细胞 (DC) 的激活参与自身免疫反应的发病机制。本研究旨在探讨白藜芦醇（一种具有免疫耐受作用的多酚抗氧化剂化合物）是否能够抵抗 AGE/RAGE 相互作用在 DC 上引发的机制。通过免疫化学和细胞荧光检测，我们证明了体外用人单核细胞来源的 DC 用白藜芦醇预处理可防止 DC 对葡萄糖处理的白蛋白（AGE-白蛋白）的激活。我们发现白藜芦醇对 DC 表面成熟标志物和 RAGE 的上调具有抑制作用，可抑制促炎细胞因子的表达、共刺激能力的上调、丝裂原激活蛋白激酶 (MAPK) 和 NF-κB 在 AGE-白蛋白刺激的 DC 中的激活。我们认为，白藜芦醇通过破坏 DC 上的 AGE/RAGE 信号通路，可能预防或减少衰老过程中对自身分子的反应性增加。
