首页> 外文期刊>The Journal of Nutritional Biochemistry >Resveratrol down-regulates interferon- gamma-inducible inflammatory genes in macrophages: molecular mechanism via decreased STAT-1 activation.
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Resveratrol down-regulates interferon- gamma-inducible inflammatory genes in macrophages: molecular mechanism via decreased STAT-1 activation.

机译:白藜芦醇下调巨噬细胞中干扰素-γ诱导的炎症基因:STAT-1激活降低的分子机制。

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Resveratrol (trans-3,4',5-trihydroxystilbene) is one of nonflavonoid polyphenolic phytoalexins found in various plant species, a number of which are components of human diet including grapes and red wines. Resveratrol has exerted several beneficial effects with anti-inflammation, cardioprotection and cancer chemoprevention. However, its mechanisms of action are not completely understood. In this study, we investigated effects of resveratrol on inflammatory gene expression in interferon (IFN)- gamma alone-stimulated macrophages and proposed a molecular basis underlying the action. Resveratrol inhibited IFN- gamma-induced production of nitric oxide (NO), IFN- gamma-inducible protein-10 (IP-10), or the monokine induced by IFN- gamma (MIG) in RAW 264.7 macrophages and also that of NO in primary macrophages derived from bone marrows of C3H/HeJ (toll-like receptor-4--/--) mice. Moreover, resveratrol diminished IFN- gamma-induced protein levels of inducible NO synthase (iNOS), attenuated mRNA levels of iNOS, IP-10 or MIG as well as inhibited IFN- gamma-induced promoter activity of iNOS gene, indicating that the phytoalexin could down-regulate inflammatory genes at the transcription level. To understand a mechanism of the action, we tested resveratrol could affect the signal transducers and activation of transcription-1 (STAT-1), a pivotal transcription factor in IFN- gamma-induced expression of inflammatory genes. Resveratrol inhibited IFN- gamma-induced transcriptional activity of STAT-1 in macrophages and also IFN- gamma-induced Tyr701 or Ser727 phosphorylation of STAT-1. We then focused on protein kinases upstream STAT-1 phosphorylation. Resveratrol inhibited IFN- gamma-induced activation of Janus kinase-2 (JAK-2) and also the extracellular signal-regulated kinase, in which JAK-2 was more sensitive. Taken together, this study proposes a new mechanism of resveratrol, blocking JAK/STAT-1 pathway that controls inflammatory responses in IFN- gamma-activated macrophages. All rights reserved, Elsevier.
机译:白藜芦醇(反式-3,4',5-三羟基sti)是一种在各种植物中发现的非黄酮类多酚类植物抗毒素,其中许多是人类饮食中的成分,包括葡萄和红酒。白藜芦醇在消炎,心脏保护和癌症化学预防方面发挥了多种有益作用。但是,其作用机理尚未完全了解。在这项研究中,我们调查了白藜芦醇对干扰素(IFN)-γ单独刺激的巨噬细胞中炎性基因表达的影响,并提出了该作用的分子基础。白藜芦醇抑制RAW 264.7巨噬细胞中IFN-γ诱导的一氧化氮(NO),IFN-γ诱导性蛋白10(IP-10)或IFN-γ(MIG)诱导的单核因子的生成,以及原代巨噬细胞来自C3H / HeJ(toll-like receptor-4 -/-)小鼠的骨髓。此外,白藜芦醇降低了IFN-γ诱导的一氧化氮合酶(iNOS)的蛋白水平,减弱了iNOS,IP-10或MIG的mRNA水平,并抑制了IFN-γ诱导的iNOS基因的启动子活性,表明该植物抗毒素可以在转录水平下调炎症基因。为了了解其作用机理,我们测试了白藜芦醇可能会影响信号转导和转录1(STAT-1)的激活,转录1(STAT-1)是IFN-γ诱导的炎症基因表达的关键转录因子。白藜芦醇抑制IFN-γ诱导的巨噬细胞STAT-1的转录活性,也抑制IFN-γ诱导的Tyr 701 或Ser 727 的STAT-1磷酸化。然后,我们专注于上游STAT-1磷酸化的蛋白激酶。白藜芦醇抑制了IFN-γ诱导的Janus激酶2(JAK-2)的活化,也抑制了细胞外信号调节激酶,其中JAK-2更为敏感。综上所述,这项研究提出了白藜芦醇的新机制,该机制阻断了控制IFN-γ活化巨噬细胞中炎症反应的JAK / STAT-1途径。保留所有权利,Elsevier。

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