Inhibition of autoantigen expression by (-)-epigallocatechin-3-gallate (the Major Constituent of Green Tea) in normal human cells
Inhibition of autoantigen expression by (-)-epigallocatechin-3-gallate (the Major Constituent of Green Tea) in normal human cells
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DOI：
10.1124/jpet.105.090399
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发表时间：
2005-11-01
影响因子：
3.5
通讯作者：
Schuster, G
中科院分区：
文献类型：
--
作者：
Hsu, S;Dickinson, DP;Schuster, G
自身免疫性疾病的特征是靶细胞的炎症和凋亡导致组织破坏，部分是由可能过度表达的针对正常细胞成分(自身抗原)的自身抗体介导的。例如，针对自身抗原SS-A/Ro和SS-B/La的抗体是系统性红斑狼疮和干燥综合征的主要标志。最近，在动物身上的研究表明，饮用绿茶可能会降低一些自身免疫性疾病的严重程度，但其机制尚不清楚。在这里，我们试图确定最丰富的绿茶多酚，(-)-表没食子儿茶素没食子酸酯(EGCG)，是否影响人类细胞的自身抗原表达。将培养的正常人原代表皮角质形成细胞和永生化的人唾液腺泡细胞系与100亩EGCG(生理上可达到的局部或口服给药水平)孵育不同时间，然后用基因芯片分析、逆转录聚合酶链式反应和Western blotting分析几种主要自身抗原候选者的表达。EGCG抑制主要自身抗原的转录和翻译，包括SS-B/La、SS-A/Ro、Colin、DNA拓扑异构酶I和α-fodrin。这些发现，加上绿茶的抗炎和抗凋亡作用，表明绿茶多酚可以作为对抗人类自身免疫性疾病的新方法的重要组成部分。
Autoimmune disorders, characterized by inflammation and apoptosis of target cells leading to tissue destruction, are mediated in part by autoantibodies against normal cellular components (autoantigens) that may be overexpressed. For example, antibodies against the autoantigens SS-A/Ro and SS-B/La are primary markers for systemic lupus erythematosus and Sjogren's syndrome. Recently, studies in animals demonstrated that green tea consumption may reduce the severity of some autoimmune disorders, but the mechanism is unclear. Herein, we sought to determine whether the most abundant green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), affects autoantigen expression in human cells. Cultures of pooled normal human primary epidermal keratinocytes and of an immortalized human salivary acinar cell line were incubated with 100 mu M EGCG (a physiologically achievable level for topical application or oral administration) for various time periods and then analyzed by cDNA microarray analysis, reverse transcriptionpolymerase chain reaction, and Western blotting for expression of several major autoantigen candidates. EGCG inhibited the transcription and translation of major autoantigens, including SS-B/La, SS-A/Ro, coilin, DNA topoisomerase I, and alpha-fodrin. These findings, taken together with green tea's anti-inflammatory and antiapoptotic effects, suggest that green tea polyphenols could serve as an important component in novel approaches to combat autoimmune disorders in humans.