EGCG一種強力免疫調節劑的茶成分可以減少香菸中濃縮物所誘發之抗－Legionella pneumophila活性之抑制和降低肺泡巨噬細胞之細胞激素反應

Epigallocatechin Gallate, a Potential Immunomodulatory Agent of Tea Components, Diminishes Cigarette Smoke Condensate-Induced Suppression of Anti-Legionella pneumophila Activity and Cytokine Responses of Alveolar Macrophages

劉紹毅 ； Kazuto Matsunage ； Thomas W. Klein ； Herman Friedman ； Yoshimasa Yamamoto

《中華民國血液淨化醫學會雜誌》 14卷3-4期 (2009/12) Pp. 79-81

https://doi.org/10.30024/JFBPS.200912.0017

摘要

即使目前已知抽煙對於肺部之免疫反應會有所抑制，可是香菸中的成分對呼吸道感染之影響所知並不多。在本研究中，香菸中之濃縮物(cigarette smoke condensate, CSC)之在肺泡巨噬細胞中，對於細菌之複製和此巨噬細胞對於感染之免疫反應影響將加以探討。更進一步來說，EGCG為兒茶素在茶葉中之主要成分，其可能其有免疫治療效果，我們檢測對於CSC所誘發之抗菌作用力(antimicrobial activity)和對於肺泡巨噬細胞之免疫反應的影響。我們利用CSC處理鼠之肺泡巨噬細胞系(MH-S)，會明顯的增進巨噬細胞中之Legionella pneumophila的增殖和選擇性的使藉由細菌感染所誘發之介白質－6(IL-6)與腫瘤壞死因子－α(tumor necrosis factor-α; TNF-α)生成作用之向下調整。使用EGCG處理巨噬細胞時，不僅可以克服將CSC所誘發之抗菌活性的抑制作用，而且可以強化巨噬細胞對於是感染之抗性(resistance)。CSC抑制IL-6及TNF-α的生成作用，EGCG籍由使巨噬細胞對於感染的反應也可以顯著增加之IL-6與TNF-α生成作用向上調節。由利用外源性TNF-α的處理和利用anti-TNF-α與anti-gamma-interferon(IFN-γ)抗體中和性處理，以及檢測IFN-γ mRNA濃度之方式探討的結果指出，EGCG可將被CSC所抑制的巨噬細胞致活，而可用來抑制Lipneumophila之生長，此乃藉由EGCG可使TNF-α與TFN-γ生成作用向上調節。因此，這個研究結果顯示出CSC可選擇性地改變巨噬細胞對L. pneumophila感染之免疫反應和是導致在巨噬細胞中細菌增殖的增加。除此之外，兒茶素中之EGCG對於肺泡巨噬細胞的影響，可以降低CSC所造成之抑制作用。

並列摘要

Even though cigarette smoking has been shown to suppress immune responses in the lungs, little is known about the effect of cigarette smoke components on respiratory infections. In the present study, the effects of cigarette smoke condensate (CSC) on bacterial replication in alveolar macrophages and the immune responses of macrophages to infection were examined. Furthermore, a possible immunotherapeutic effect of epigallocatechin gallate (EGCg), a major form of tea catechins, on the CSC-induced suppression of antimicrobial activity and immune responses of alveolar macrophages was also determined. The treatment of murine alveolar macrophage cell line (MH-S) cells with CSC significantly enhanced the replication of Legionella pneumophila in macropbages and selectively down-regulated the production of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) induced by bacterial infection. The treatment of macrophages with EGCg not only overcame the CSC-induced suppression of antimicrobial activity but also strengthened the resistance of macrophages to infection. EGCg also markedly up-regulated the CSC-suppressed IL-6 and TNF-α production by macrophages in response to infection. The results of exogenous TNF-α treatment and neutralization treatment with anti-TNF-α and anti-gamma-interferon (IFN-γ) antibodies and the determination of IFN-γ mRNA levels indicate that CSC-suppressed macrophages can be activated by EGCg to inhibit L. pneumophila growth by up-regulation of TNF-α and IFN-γ production. Thus, this study revealed that CSC selectively alters the immune responses of macrophages to L. pneumophila infection and leads to an enhancement of bacterial replication in macrophages. In addition, the tea catechin EGCg can diminish such suppressive effects of CSC on alveolar macrophages.