一種源自綠茶多酚～EGCG在培養的呼吸道上細胞中依賴IL-1ß促發炎性細胞信號傳遞作用之抑制

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

劉紹毅 ； Derek S. Wheeler ； John D. Catravas ； Kelli Odoms ； Alvin Denenberg ； Vivek Malhotra ； Hector R. Wong

《中華民國血液淨化醫學會雜誌》 14卷3-4期 (2009/12) Pp. 88-89

https://doi.org/10.30024/JFBPS.200912.0021

摘要

綠茶中之多酚成分，如EGCG具強力之抗發炎作用性質。先前我們的報告指出EGCG可將TNF-α-媒介之NFkB路徑活化作用加以抑制，部分出自EGCG對IkB kinase(IKK)之抑制。IL-1β刺激可透過不同之信號傳遞路徑(signal transduction pathway)也可以將NFkB路徑活化。因此，我們的假設認為EGCG將IL-1β媒介之NFkB路徑活化作用抑制。因為IL-8之基因表現，此種IL-8為主要之人類中性球化學趨化劑(human neutrophil chemoattractant)，它是依賴著NFkB之活化作用，故再將人類肺之上皮(A549)細胞，以人類IL-1β加以處理來當作IL-1β信號傳遞模式時，可看到IL-8之基因表現。EGCG明顯的可以將由IL-1β-媒介之IL-1β接受體相關激酶(IRAK)之分解(degradation)及出自IRAK減化下游之信號事件抑制：亦就是發生IKK活化、IkBα分解和NFkB活化被EGCG所抑制。除此之外，EGCG可將NFkB之p65 subunit之磷酸化抑制（有人報告NFkB為p50+p65 dimer，其會以p65 subunit之N-terminus與IKB相關結）。此種來自EGCG之抑制功能之結果，可因有IL-8基因表現之抑制作用而得到証據。因此，在體外試驗中綠茶多酚EGCG為IL-1β信號傳遞之強力抑制劑。此作用之近端的作用機轉(proximal mechanisms)會涉及IRAK-dependent信號與p65磷酸化之抑制作用。

並列摘要

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-KB) pathway, partly through inhibition of 1κB 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-1 β signal transduction. The EGCG markedly inhibited IL-1ß- mediated IL-1β recepter associated kinase (IRAK) degradation and the signaling events downstream from IRAK degradation: IKK activation, IκB α degradation, and-NFκB 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-1βsignal transduction in vitro. The proximal mechanisms of this effect involve inhibition of IRAK-dependent signaling and phosphorylation of p65.