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绿茶通过下调信号转导子和转录激活子-1α的激活来抑制人类诱导型一氧化氮合酶的表达。

Green tea inhibits human inducible nitric-oxide synthase expression by down-regulating signal transducer and activator of transcription-1alpha activation.

作者信息

Tedeschi Elisa, Menegazzi Marta, Yao Ying, Suzuki Hisanori, Förstermann Ulrich, Kleinert Hartmut

机构信息

Biochemistry Section, Department of Neuroscience and Vision, University of Verona, Verona, Italy.

出版信息

Mol Pharmacol. 2004 Jan;65(1):111-20. doi: 10.1124/mol.65.1.111.

DOI:10.1124/mol.65.1.111
PMID:14722242
Abstract

Green tea has been reported to show anti-inflammatory properties because of its inhibitory effects on the expression of several pro-inflammatory genes. Because the inducible nitricoxide synthase (iNOS) plays an important role in chronic inflammatory diseases, we have focused our attention on the regulation of iNOS expression by green tea in two different human epithelial cell lines, alveolar A549/8 and colon DLD-1 cells. With the use of electrophoretic mobility shift assays, we found a green tea-mediated down-regulation of the DNA binding activity of the transcription factor signal transducer and activator of transcription-1alpha (STAT-1alpha), but not of nuclear factor-kappaB. This down-regulation of the STAT-1alpha DNA binding was shown to result from reduced tyrosine phosphorylation of the STAT-1alpha protein and not from antioxidative effects of the green tea extract. Green tea extract inhibited human iNOS expression in a concentration-dependent manner, quantified in terms of iNOS mRNA, iNOS protein, and nitric oxide production in both cell lines. This inhibitory effect of green tea resulted from transcriptional inhibition as shown in reporter gene experiments. These data suggest that green tea extracts may be promising at least as an auxiliary anti-inflammatory principle in chronic inflammatory diseases.

摘要

据报道,绿茶具有抗炎特性,因为它对几种促炎基因的表达具有抑制作用。由于诱导型一氧化氮合酶(iNOS)在慢性炎症疾病中起重要作用,我们将注意力集中在绿茶对两种不同的人上皮细胞系(肺泡A549/8细胞和结肠DLD-1细胞)中iNOS表达的调节上。通过使用电泳迁移率变动分析,我们发现绿茶介导转录因子信号转导子和转录激活子-1α(STAT-1α)的DNA结合活性下调,但不影响核因子-κB。STAT-1α DNA结合的这种下调被证明是由于STAT-1α蛋白酪氨酸磷酸化减少,而不是绿茶提取物的抗氧化作用。绿茶提取物以浓度依赖方式抑制人iNOS表达,这通过两种细胞系中的iNOS mRNA、iNOS蛋白和一氧化氮产生来定量。如报告基因实验所示,绿茶的这种抑制作用是由转录抑制引起的。这些数据表明,绿茶提取物至少作为慢性炎症疾病中的一种辅助抗炎成分可能很有前景。

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