title: Epigallocatechin-3-gallate, a green tea-derived polyphenol, inhibits IL-1 beta-dependent proinflammatory signal transduction in cultured respiratory epithelial cells.
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-alpha (TNF-alpha)-mediated activation of the nuclear factor-kappa B (NF-kappa B) pathway, partly through inhibition of I kappa B kinase (IKK). The NF-kappa B pathway may also be activated in response to interleukin-1 beta (IL-1 beta) stimulation through a distinct signal transduction pathway. We therefore hypothesized that EGCG inhibits IL-1 beta-mediated activation of the NF-kappa B pathway. Because the gene expression of interleukin-8 (IL-8), the major human neutrophil chemoattractant, is dependent on activation of NF-kappa B, IL-8 gene expression in human lung epithelial (A549) cells treated with human IL-1 beta was used as a model of IL-1 beta signal transduction. The EGCG markedly inhibited IL-1 beta-mediated IL-1 beta receptor-associated kinase (IRAK) degradation and the signaling events downstream from IRAK degradation: IKK activation, I kappa B alpha degradation, and NF-kappa B activation. In addition, EGCG inhibited phosphorylation of the p65 subunit of NF-kappa 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-1 beta signal transduction in vitro. The proximal mechanisms of this effect involve inhibition of IRAK-dependent signaling and phosphorylation of p65.
authors.affiliation: Section of Critical Care Medicine, Children's Medical Center, Medical College of Georgia, Augusta, GA 30912, USA. dewheeler@mcg.edu
authors.forename: Derek S
authors.initials: DS
authors.lastname: Wheeler
authors.forename: John D
authors.initials: JD
authors.lastname: Catravas
authors.forename: Kelli
authors.initials: K
authors.lastname: Odoms
authors.forename: Alvin
authors.initials: A
authors.lastname: Denenberg
authors.forename: Vivek
authors.initials: V
authors.lastname: Malhotra
authors.forename: Hector R
authors.initials: HR
authors.lastname: Wong
mesh_terms: D000893:Anti-Inflammatory Agents / Q000032:analysis / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D051550:I-kappa B Kinase; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000502:physiology*; D053592:Interleukin-1 Receptor-Associated Kinases; D016209:Interleukin-8 / Q000235:genetics; D007527:Isoenzymes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D010636:Phenols / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D059808:Polyphenols; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020545:Respiratory Mucosa / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013662:Tea / Q000737:chemistry*; D051996:Transcription Factor RelA
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D018836:Inflammation Mediators; D007375:Interleukin-1; D016209:Interleukin-8; D007527:Isoenzymes; D016328:NF-kappa B; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D051996:Transcription Factor RelA; D002392:Catechin; C045651:epigallocatechin gallate; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human