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Nutrient-Gene Interactions

Epigallocatechin-3-gallate, a Green Tea–Derived Polyphenol, Inhibits IL-1ß-Dependent Proinflammatory Signal Transduction in Cultured Respiratory Epithelial Cells^1,2

Derek S. Wheeler³, John D. Catravas^*, Kelli Odoms, Alvin Denenberg, Vivek Malhotra and Hector R. Wong

Section of Critical Care Medicine, Children’s Medical Center, and ^* Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912; and Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, and Children’s Hospital Research Foundation, Cincinnati, OH 45229

³To whom correspondence should be addressed. E-mail: dewheeler{at}mcg.edu.

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- (TNF-)–mediated activation of the nuclear factor-B (NF-B) pathway, partly through inhibition of IB kinase (IKK). The NF-B pathway may also be activated in response to interleukin-1ß (IL-1ß) stimulation through a distinct signal transduction pathway. We therefore hypothesized that EGCG inhibits IL-1ß-mediated activation of the NF-B pathway. Because the gene expression of interleukin-8 (IL-8), the major human neutrophil chemoattractant, is dependent on activation of NF-B, IL-8 gene expression in human lung epithelial (A549) cells treated with human IL-1ß was used as a model of IL-1ß signal transduction. The EGCG markedly inhibited IL-1ß–mediated IL-1ß receptor–associated kinase (IRAK) degradation and the signaling events downstream from IRAK degradation: IKK activation, IB degradation, and NF-B activation. In addition, EGCG inhibited phosphorylation of the p65 subunit of NF-B. 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-1ß signal transduction in vitro. The proximal mechanisms of this effect involve inhibition of IRAK-dependent signaling and phosphorylation of p65.

KEY WORDS: • transcription factors • inflammation • signal transduction • chemokines • polyphenols

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