A Green Tea-Derived Polyphenol, Epigallocatechin-3-Gallate, Inhibits IκB Kinase Activation and IL-8 Gene Expression in Respiratory Epithelium

Chen, Philip C.; Wheeler, Derek S.; Malhotra, Vivek; Odoms, Kelli; Denenberg, Alvin G.; Wong, Hector R.

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-α (TNF-α)-mediated expression of the IL-8 gene in A549 cells. EGCG inhibited TNF-α-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-α-mediated activation of the IL-8 promoter in cells transiently transfected with an IL-8 promoter-luciferase reporter plasmid. In addition, EGCG inhibited TNF-α-mediated activation of IκB kinase and subsequent activation of the IκBα/NF-κB 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 IκB kinase activation.