Nutritionally relevant concentrations of resveratrol and hydroxytyrosol mitigate oxidative burst of human granulocytes and monocytes and the production of pro-inflammatory mediators in LPS-stimulated RAW 264.7 macrophages
Nutritionally relevant concentrations of resveratrol and hydroxytyrosol mitigate oxidative burst of human granulocytes and monocytes and the production of pro-inflammatory mediators in LPS-stimulated RAW 264.7 macrophages
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DOI：
10.1016/j.intimp.2016.12.012
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发表时间：
2017-02-01
影响因子：
5.6
通讯作者：
Luceri, Cristina
中科院分区：
文献类型：
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作者：
Bigagli, Elisabetta;Cinci, Lorenzo;Luceri, Cristina
生物活性酚类化合物的健康益处已经在体外进行了大量研究，其浓度超过体内可达到的浓度。我们通过体外炎症模型研究并比较了生理相关浓度下白藜芦醇、羟基酪醇和橄榄苦苷的抗炎作用。用肉豆酸酯佛波刺激人粒细胞和单核细胞，测定白藜芦醇、羟基酪醇和橄榄苦苷对氧化破裂和CD11b表达的抑制能力。用LPS （1 μ g/ml）刺激巨噬细胞RAW 264.7，暴露于白藜芦醇、羟基酪醇和橄榄醇（5和10 μ M）中18 h，评估巨噬细胞一氧化氮（NO）、前列腺素E2 （PGE2）水平、COX-2、iNOS、TNF α、IL-1 β和miR-146a的表达和转录因子Nrf2的激活。并通过LPS刺激6 h后巨噬细胞中PGE2、COX-2和IL-1 β的表达水平，探讨其协同效应。PGE2和COX-2在人单核细胞中的表达也被评估。所有化合物均以浓度依赖的方式抑制粒细胞氧化爆发，白藜芦醇和羟基酪醇也显著抵消CD11b的表达。人体单核细胞氧化爆发的测量也产生了类似的效果，白藜芦醇更活跃。在LPS刺激的RAW 264.7中，羟基酪醇和白藜芦醇抑制NO和PGE2的产生，但在18小时内没有降低iNOS、TNF α或IL-1 β基因的表达。白藜芦醇在18小时后轻微降低COX-2的表达，但在6小时后没有降低PGE2的表达，但在6小时后降低了PGE2的水平。白藜芦醇和羟基酪醇10 μ M诱导NRf2核易位并降低了LPS处理的RAW 264.7中miR-146a的表达。总的来说，我们报道了低营养相关浓度的白藜芦醇和羟基酪醇的抗炎作用，包括抑制粒细胞和单核细胞的激活，调节miR-146a的表达和Nrf2的激活。定期膳食摄入白藜芦醇和羟基酪醇可能是控制炎症性疾病的有益补充策略。(C) 2016 Elsevier B.V.版权所有
The health benefits of bio-active phenolic compounds have been largely investigated in vitro at concentrations which exceed those reachable in vivo. We investigated and compared the anti-inflammatory effects of resveratrol, hydroxytyrosol and oleuropein at physiologically relevant concentrations by using in vitro models of inflammation.Human granulocytes and monocytes were stimulated with phorbol myristate acetate (PMA) and the ability of resveratrol, hydroxytyrosol and oleuropein to inhibit the oxidative burst and CD11b expression was measured. Nitric oxide (NO), prostaglandin E2 (PGE2) levels, COX-2, iNOS, TNF alpha, IL-1 beta and miR-146a expression and activation of the transcription factor Nrf2 were evaluated in macrophages RAW 264.7 stimulated with LPS (1 mu g/ml) for 18 h, exposed to resveratrol, hydroxytyrosol and oleuropein (5 and 10 mu M). Synergistic effects were explored as well, together with the levels of PGE2, COX-2 and IL-1 beta expression in macrophages after 6 h of LPS stimulation. PGE2 and COX-2 expression were also assessed on human monocytes.All the tested compounds inhibited granulocytes oxidative burst in a concentration dependent manner and CD11b expression was also significantly counteracted by resveratrol and hydroxytyrosol. The measurement of oxidative burst in human monocytes produced similar effects being resveratrol more active. Hydroxytyrosol and resveratrol inhibited the production of NO and PGE2 but did not reduce iNOS, TNF alpha or IL-1 beta gene expression in LPS-stimulated RAW 264.7 for 18 h. Resveratrol slightly decreased COX-2 expression after 18 h but not after 6 h, but reduced PGE2 levels after 6 h. Resveratrol and hydroxytyrosol 10 mu M induced NRf2 nuclear translocation and reduced miR-146a expression in LPS treated RAW 264.7.Overall, we reported an anti-inflammatory effect of resveratrol and hydroxytyrosol at low, nutritionally relevant concentrations, involving the inhibition of granulocytes and monocytes activation, the modulation of miR-146a expression and the activation of Nrf2. A regular dietary intake of resveratrol and hydroxytyrosol may be a useful complementary strategy to control inflammatory diseases. (C) 2016 Elsevier B.V. All rights reserved.