A green tea-derived polyphenol, epigallocatechin-3-gallate, inhibits IkappaB kinase activation and IL-8 gene expression in respiratory epithelium.
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.
Chen
Philip C
PC
Division of Critical Care Medicine, Children's Hospital Medical Center and Children's Hospital Research Foundation, Cincinnati, OH 45244, USA.
Wheeler
Derek S
DS
Malhotra
Vivek
V
Odoms
Kelli
K
Denenberg
Alvin G
AG
Wong
Hector R
HR
D000975:Antioxidants / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids; D006801:Humans; D051550:I-kappa B Kinase; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D013662:Tea / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000975:Antioxidants; D005419:Flavonoids; D016209:Interleukin-8; D016328:NF-kappa B; D010636:Phenols; D011108:Polymers; D012333:RNA, Messenger; D013662:Tea; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; C045651:epigallocatechin gallate; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human