Naturally occurring polyphenolic antioxidants modulate IgE-mediated mast cell activation

Naturally occurring polyphenolic antioxidants modulate IgE-mediated mast cell activation
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DOI:
10.1046/j.1365-2567.2000.00045.x
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发表时间:
2000-08-01
期刊:
影响因子:
6.4
通讯作者:
Mohammed, U
Mohammed, U
中科院分区:
医学2区
文献类型:
--
作者:
Chen, SS;Gong, J;Mohammed, U

文献摘要

被引文献

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活性氧(ROS)可以调节多种激酶、磷酸酶和转录因子的活性。利用反相高压液相色谱法和质谱法测定了无烟叶提取物小分子组分中主要的多酚类抗氧化剂为芦丁和绿原酸。采用羧基二氯荧光素(DCFH-DA)荧光活化细胞分选(FACS)技术,在510 nm处测定静息与抗原免疫球蛋白E (IgE)激发小鼠肥大细胞的细胞内ROS水平。抗原刺激后,在ige致敏的肥大细胞中观察到ROS生成增强。芦丁和CGA可降低抗原ige激活肥大细胞中的ROS水平。同时,它们也深刻地抑制了这些活化肥大细胞释放的组胺。相反,芦丁和CGA增加了可诱导的细胞因子信息,即白细胞介素(IL)-10、IL-13、干扰素γ (ifn - γ)、IL-6和肿瘤坏死因子α。(tnf - α)在抗原刺激后ige致敏肥大细胞中的表达。本研究表明,烟草多酚类抗氧化剂可抑制细胞内活性氧,对抗原ige激活肥大细胞的两种效应功能有不同的影响。该模型系统可用于确定多酚的分子靶点。这些多酚类抗氧化剂对体内ige介导的过敏的潜在作用取决于它们对肥大细胞活化的不同影响的平衡。
Reactive oxygen species (ROS) are known to modulate activities of a host of kinases, phosphatases and transcription factors. Rutin and chlorogenic acid (CGA) are the major polyphenolic antioxidants present in the small molecular fraction of smokeless tobacco leaf extracts, as ascertained by reverse-phase high-pressure liquid chromatography (HPLC) and mass spectrometry. Levels of intracellular ROS in resting versus antigen-immunoglobulin E (IgE)-challenged murine mast cells were measured at 510 nm by fluorescence-activated cell sorting (FACS) using carboxy-dichlorofluorescein (DCFH-DA). Enhanced ROS production was observed in IgE-sensitized mast cells following antigenic challenge. Rutin and CGA reduced ROS levels in antigen-IgE-activated mast cells. Concomitantly, they also profoundly inhibited histamine release by these activated mast cells. In contrast, rutin and CGA augmented the inducible cytokine messages, i.e. interleukin (IL)-10, IL-13, interferon-gamma (IFN-gamma), IL-6 and tumour necrosis factor-alpha. (TNF-alpha) in IgE-sensitized mast cells following antigen challenge. This study indicates that tobacco polyphenolic antioxidants that quench intracellular ROS, differentially affect two effector functions of antigen-IgE-activated mast cells. This model system may be employed to determine the molecular target of polyphenols. The potential role of these polyphenolic antioxidants on IgE-mediated allergy in vivo depends on a balance of their differential effects on mast cell activation.