Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-κB, activator protein-1, and apoptosis:: Potential role of reactive oxygen intermediates and lipid peroxidation
Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-κB, activator protein-1, and apoptosis:: Potential role of reactive oxygen intermediates and lipid peroxidation
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DOI：
10.4049/jimmunol.164.12.6509
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发表时间：
2000-06-15
影响因子：
4.4
通讯作者：
Aggarwal, BB
中科院分区：
文献类型：
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作者：
Manna, SK;Mukhopadhyay, A;Aggarwal, BB
白藜芦醇（反式-3，4 '，5-三羟基芪）是一种多酚类植物抗毒素，存在于葡萄、果实和杂草虎杖（Polygonum cuspidatum）的根提取物中，具有抗炎、细胞生长调节和抗癌作用。这种化学物质如何产生这些作用尚不清楚，但它可能通过抑制NP-κ B起作用，NP-κ B是一种核转录因子，调节炎症、细胞保护和致癌作用中涉及的各种基因的表达。本研究观察了白藜芦醇对多种炎症因子诱导的NF-κ B活化的影响。白藜芦醇以剂量和时间依赖的方式阻断TNF诱导的NF-κ B活化。白藜芦醇还抑制TNF诱导的NF-κ B B p65亚基的磷酸化和核转位，以及NF-κ B依赖性报告基因转录。白藜芦醇对TNF诱导的NF-κ B活化的抑制不仅限于髓样细胞（U-937）;还在淋巴（Jurkat）和上皮（HeLa和H4）细胞中观察到。白藜芦醇还能抑制PMA、LPS、H_2O_2、冈田酸和神经酰胺诱导的NF-κ B活化，抑制NF-κ B的同时也抑制AP-1的活化。白藜芦醇还能抑制TNF诱导的丝裂原活化蛋白激酶激酶（MAPK）和c-Jun N-末端激酶（c-Jun N-terminal kinase）的活化，并能消除TNF诱导的细胞毒性和caspase的活化。白藜芦醇能抑制TNF诱导的活性氧中间产物的产生和脂质过氧化反应。因此，白藜芦醇的抗癌、抗炎和生长调节作用可能部分归因于抑制NF-κ B和AP-1及其相关激酶的活化。
Resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenolic phytoalexin found in grapes, fruits, and root extracts of the weed Polygonum cuspidatum, exhibits anti-inflammatory, cell growth-modulatory, and anticarcinogenic effects. How this chemical produces these effects is not known, but it may work by suppressing NP-kappa B, a nuclear transcription factor that regulates the expression of various genes involved in inflammation, cytoprotection, and carcinogenesis. In this study, we investigated the effect of resveratrol on NF-kappa B activation induced by various inflammatory agents, Resveratrol blocked TNF-induced activation of NF-kappa B in a dose- and time-dependent manner. Resveratrol also suppressed TNF-induced phosphorylation and nuclear translocation of the p65 subunit of NF-kappa B, and NF-kappa B-dependent reporter gene transcription, Suppression of TNF-induced NF-kappa B activation by resveratrol was not restricted to myeloid cells (U-937); it was also observed in lymphoid (Jurkat) and epithelial (HeLa and H4) cells. Resveratrol also blocked NF-kappa B activation induced by PMA, LPS, H2O2, okadaic acid, and ceramide, The suppression of NF-kappa B coincided with suppression of AP-1, Resveratrol also inhibited the TNF-induced activation of mitogen-activated protein kinase kinase and c-Jun N-terminal kinase and abrogated TNF-induced cytotoxicity and caspase activation. Both reactive oxygen intermediate generation and lipid peroxidation induced by TNF were suppressed by resveratrol. Resveratrol's anticarcinogenic, anti-inflammatory, and growth-modulatory effects may thus be partially ascribed to the inhibition of activation of NF-kappa B and AP-1 and the associated kinases.