Epigallocatechin-3-gallate, a Green Tea-Derived Polyphenol, Inhibits IL-1β-Dependent Proinflammatory Signal Transduction in Cultured Respiratory Epithelial Cells

Derek S. Wheeler*, John D. Catravas, Kelli Odoms, Alvin Denenberg, Vivek Malhotra, Hector R. Wong

*Corresponding author for this work

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

Polyphenolic components of green tea, such as epigallocatechin-3-gallate (EGCG), have potent anti-inflammatory properties. We previously showed that EGCG inhibits tumor necrosis factor-α (TNF-α)-mediated activation of the nuclear factor-κB (NF-κB) pathway, partly through inhibition of IκB kinase (IKK). The NF-κB pathway may also be activated in response to interleukin-1β (IL-1β) stimulation through a distinct signal transduction pathway. We therefore hypothesized that EGCG inhibits IL-1β-mediated activation of the NF-κB pathway. Because the gene expression of interleukin-8 (IL-8), the major human neutrophil chemoattractant, is dependent on activation of NF-κB, IL-8 gene expression in human lung epithelial (A549) cells treated with human IL-1β was used as a model of IL-1β signal transduction. The EGCG markedly inhibited IL-1β-mediated IL-1β receptor-associated kinase (IRAK) degradation and the signaling events downstream from IRAK degradation: IKK activation, IκBα degradation, and NF-κB activation. In addition, EGCG inhibited phosphorylation of the p65 subunit of NF-κB. The functional consequence of this inhibition was evident by inhibition of IL-8 gene expression. Therefore, the green tea polyphenol EGCG is a potent inhibitor of IL-1β signal transduction in vitro. The proximal mechanisms of this effect involve inhibition of IRAK-dependent signaling and phosphorylation of p65.

Original languageEnglish (US)
Pages (from-to)1039-1044
Number of pages6
JournalJournal of Nutrition
Volume134
Issue number5
DOIs
StatePublished - May 2004

Keywords

  • Chemokines
  • Inflammation
  • Polyphenols
  • Signal transduction
  • Transcription factors

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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