Resveratrol (Res), a natural polyphenol compound found in grapes and red wine, has been shown to exhibit anti-inflammatory, antioxidant, and anticarcinogenic effects. However, proinflammatory/tumor-promoting properties of Res have also been reported, rendering the polyphenol's reported therapeutic benefits less convincing and controversial. To evaluate the underlying plausible factors contributing to the differential immunomodulatory effects imparted by Res, herein, we investigated, at both physiological and pharmacological doses, the in vitro effects of Res on cell survival/proliferation, inflammatory genes, and cytokine production in human monocytic cell line (THP-1) and phorbol 12-myristate 13-acetate differentiated human THP-1-derived macrophages. We hypothesized that the differential effects observed in monocytes and macrophages may largely depend on dietary vs pharmacological doses of Res, duration of treatment, and the target cells it acts upon. Our data showed that Res, at physiological concentrations, inhibited proliferation of THP-1 monocytes with S phase arrest. On the other hand, at pharmacological concentrations, Res induced cell apoptosis and caused G0/G1 phase arrest. Additionally, Res showed differential effects on proinflammatory cytokine expression and production measured by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively, in THP-1 monocytes vs macrophages: promoting inflammation in monocytes while exhibiting anti-inflammatory effects in macrophages. Comparative analysis on Res and 2 other phytochemicals, pterostilbene and genistein, revealed that the immunomodulatory effects of Res were consistent with those observed in pterostilbene and not genistein. Our results reveal a pleiotropic immunomodulatory property of Res that is dose-time-target cell-dependent and thus serve as a caution for the use of Res in the treatment of inflammatory diseases.

中文翻译：

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白藜芦醇差异调节人 THP-1 单核细胞和巨噬细胞的免疫反应

白藜芦醇 (Res) 是一种在葡萄和红酒中发现的天然多酚化合物，已被证明具有抗炎、抗氧化和抗癌作用。然而，Res 的促炎/肿瘤促进特性也有报道，这使得所报告的多酚治疗益处缺乏说服力和争议。为了评估导致 Res 赋予不同免疫调节作用的潜在可能因素，我们在此研究了生理和药理剂量下 Res 对人单核细胞中细胞存活/增殖、炎症基因和细胞因子产生的体外影响系 (THP-1) 和佛波醇 12-肉豆蔻酸酯 13-乙酸酯分化的人 THP-1 衍生巨噬细胞。我们假设在单核细胞和巨噬细胞中观察到的不同效应可能在很大程度上取决于 Res 的饮食与药理剂量、治疗持续时间及其作用的靶细胞。我们的数据显示，在生理浓度下，Res 抑制 THP-1 单核细胞的增殖，并伴有 S 期阻滞。另一方面，在药理浓度下，Res 诱导细胞凋亡并导致 G0/G1 期停滞。此外，在 THP-1 单核细胞与巨噬细胞中，通过逆转录聚合酶链反应和酶联免疫吸附测定分别测量，Res 对促炎细胞因子的表达和产生有不同的影响：促进单核细胞的炎症，同时在巨噬细胞中表现出抗炎作用。Res和其他2种植物化学物质的比较分析，紫檀芪和金雀异黄素的研究表明，Res 的免疫调节作用与在紫檀芪中观察到的一致，而不是在金雀异黄素中观察到的。我们的结果揭示了 Res 的多效性免疫调节特性，该特性是剂量-时间-靶细胞依赖性的，因此可以作为使用 Res 治疗炎症性疾病的注意事项。