Flavones mitigate tumor necrosis factor-α-induced adhesion molecule -: Upregulation in cultured human endothelial cells:: Role of nuclear factor-κB
Flavones mitigate tumor necrosis factor-α-induced adhesion molecule -: Upregulation in cultured human endothelial cells:: Role of nuclear factor-κB
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DOI：
10.1093/jn/134.5.1013
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发表时间：
2004-05-01
影响因子：
4.2
通讯作者：
Kang, YH
中科院分区：
文献类型：
--
作者：
Choi, JS;Choi, YJ;Kang, YH
黄酮类化合物已被归类为抗动脉粥样硬化剂，其可能通过阻断细胞粘附分子（CAM）的诱导来抑制单核细胞粘附至刺激的内皮。这些黄酮类化合物的抗动脉粥样硬化特征似乎与它们的化学结构有关。黄酮类化合物可能干扰炎症介质激活内皮细胞的关键信号事件。本研究检测了黄酮类化合物对TNF-α激活的人脐静脉内皮细胞（HUVEC）CAM诱导和核因子-κ B（NF-κ B）易位及DNA结合的影响。测定黄酮类化合物木樨草素和芹菜素对THP-1单核细胞与TNF-α激活的HUVEC粘附、血管细胞粘附分子-1（VCAM-1）、细胞内细胞粘附分子-1（ICAM-1）和E-选择素的蛋白表达和mRNA水平以及NF-κ B的核外观和DNA结合活性的影响。黄烷醇、黄酮醇和黄烷酮用于比较。TNF-α显著诱导HUVEC表达VCAM-1、ICAM-1和E-选择素，并增加mRNA水平。木犀草素和芹菜素抑制TNF-α诱导的THP-1粘附和VCAM-1表达的上调;这些抑制作用具有剂量依赖性。当黄酮类化合物的浓度大于或等于25 μ mol/L时，无论其抗氧化活性如何，其增加的CAM蛋白和mRNA几乎完全消失。除了黄酮醇槲皮素，黄酮类化合物没有这样的效果，槲皮素大大减弱CAM诱导。黄酮类化合物可抑制TNF-α激活的HUVEC中CAM基因启动子区含NF-κ B结合位点的核转位和DNA结合活性。黄酮类化合物对内皮细胞CAM诱导的抑制作用是通过干扰NF-κ B依赖性转录途径介导的。因此，黄酮类化合物可能阻碍涉及内皮CAM诱导的初始动脉粥样硬化事件。
Flavones have been classified as anti-atherogenic agents that inhibit monocyte adhesion to stimulated endothelium, possibly by blocking induction of cell adhesion molecules (CAM). This anti-atherogenic feature of these flavonoids appears to be related to their chemical structures. Flavones may interfere with key signaling events involved in endothelial cell activation by inflammatory mediators. This study examined the effects of flavones on the induction of CAM and the translocation and DNA binding of nuclear factor-kappaB (NF-kappaB) in TNF-alpha-activated human umbilical vein endothelial cells (HUVEC). The effects of flavones, luteolin and apigenin, on adhesion of THP-1 monocytes to the TNF-alpha-activated HUVEC, protein expression and mRNA levels of vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule-1 (ICAM-1) and E-selectin, and nuclear appearance and DNA binding activity of NF-kappaB were determined. Flavanols, flavonols, and flavanones were used for comparison. TNF-alpha significantly induced HUVEC protein expression of VCAM-1, ICAM-1, and E-selectin with increasing mRNA levels. Luteolin and apigenin inhibited the TNF-alpha-induced upregulation of THP-1 adhesion and VCAM-1 expression; these inhibitory effects were dose-dependent. The flavones at doses of greater than or equal to25 mumol/L almost completely abolished the increased CAM protein and mRNA regardless of their anti-oxidative activity. With the exception of the flavonol quercetin, flavonoids had no such effect; quercetin substantially attenuated the CAM induction. The flavones inhibited nuclear translocation and DNA binding activity of the NF-kappaB-containing binding site in the promoter region of the CAM genes in TNF-alpha-activated HUVEC. The inhibition of endothelial CAM induction by flavones is mediated by their interference with the NF-kappaB-dependent transcription pathway. Thus, the flavones may hamper initial atherosclerotic events involving endothelial CAM induction.