Chen Philip C, Wheeler Derek S, Malhotra Vivek, Odoms Kelli, Denenberg Alvin G, Wong Hector R
Division of Critical Care Medicine, Children's Hospital Medical Center and Children's Hospital Research Foundation, Cincinnati, OH 45244, USA.
Inflammation. 2002 Oct;26(5):233-41. doi: 10.1023/a:1019718718977.
Interleukin-8 (IL-8) is a principle neutrophil chemoattractant and activator in humans. There is interest in developing novel pharmacological inhibitors of IL-8 gene expression as a means for modulating inflammation in disease states such as acute lung injury. Herein we determined the effects of epigallocatechin-3-gallate (EGCG), a green tea-derived polyphenol, on tumor necrosis factor-alpha (TNF-alpha)-mediated expression of the IL-8 gene in A549 cells. EGCG inhibited TNF-alpha-mediated IL-8 gene expression in a dose response manner, as measured by ELISA and Northern blot analysis. This effect appears to primarily involve inhibition of IL-8 transcription because EGCG inhibited TNF-alpha-mediated activation of the IL-8 promoter in cells transiently transfected with an IL-8 promoter-luciferase reporter plasmid. In addition, EGCG inhibited TNF-alpha-mediated activation of IkappaB kinase and subsequent activation of the IkappaB alpha/NF-kappaB pathway. We conclude that EGCG is a potent inhibitor of IL-8 gene expression in vitro. The proximal mechanism of this effect involves, in part, inhibition of IkappaB kinase activation.
白细胞介素-8（IL-8）是人体内主要的中性粒细胞趋化因子和激活剂。人们对开发新型IL-8基因表达的药理学抑制剂作为调节诸如急性肺损伤等疾病状态下炎症的一种手段很感兴趣。在此，我们确定了表没食子儿茶素-3-没食子酸酯（EGCG），一种源自绿茶的多酚，对肿瘤坏死因子-α（TNF-α）介导的A549细胞中IL-8基因表达的影响。通过ELISA和Northern印迹分析测定，EGCG以剂量反应方式抑制TNF-α介导的IL-8基因表达。这种效应似乎主要涉及对IL-8转录的抑制，因为EGCG抑制了用IL-8启动子-荧光素酶报告质粒瞬时转染的细胞中TNF-α介导的IL-8启动子激活。此外，EGCG抑制TNF-α介导的IκB激酶激活以及随后的IκBα/NF-κB途径激活。我们得出结论，EGCG在体外是IL-8基因表达的有效抑制剂。这种效应的近端机制部分涉及对IκB激酶激活的抑制。
