Legionella pneumophila replication in macrophages inhibited by selective immunomodulatory effects on cytokine formation by epigallocatechin gallate, a major form of tea catechins

Legionella pneumophila replication in macrophages inhibited by selective immunomodulatory effects on cytokine formation by epigallocatechin gallate, a major form of tea catechins
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DOI:
10.1128/iai.69.6.3947-3953.2001
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发表时间:
2001-06-01
影响因子:
3.1
通讯作者:
Yamamoto, Y
Yamamoto, Y
中科院分区:
医学2区
文献类型:
--
作者:
Matsunaga, K;Klein, TW;Yamamoto, Y

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表没食子儿茶素没食子酸酯(EGCg)是儿茶素的主要形式,具有多种生物活性,包括抗肿瘤以及对一些病原体的抗菌活性。虽然EGCg的生物活性已被广泛研究,但其免疫学效应尚不清楚。在本研究中,EGCg调节巨噬细胞免疫功能的能力在体外嗜肺军团菌感染模型的巨噬细胞进行了检查。结果表明,EGCg对L.在巨噬细胞中以低至0.5 μ g/ml的浓度存在嗜肺菌,而对生物体没有任何直接的抗菌作用。EGCg选择性上调L.嗜肺菌感染的剂量依赖性的方式,但并没有改变IL-6的生产,即使在高剂量。还证实EGCg上调巨噬细胞γ干扰素(IFN-γ)mRNA的水平。用抗TNF-a和抗IFN-γ单克隆抗体处理巨噬细胞培养物显着消除了抗L。嗜肺细胞的活性。这些结果表明EGCg选择性地改变了巨噬细胞对L.并导致抗L.通过增强TNF-α和IFN-γ的产生介导的巨噬细胞的嗜肺细胞活性。但体外抗L.通过EGCg的嗜肺细胞活性可能不直接通过IL-10和IL-12产生调节介导。因此,本研究的结果揭示了EGCg对巨噬细胞的免疫调节作用,巨噬细胞在感染中具有关键作用。
Epigallocatechin gallate (EGCg) is a major form of tea catechin and has a variety of biological activities, including antitumor as well as antimicrobial activity against some pathogens. Although the biological activities of EGCg have been extensively studied, its immunological effects are not well known. In the present study, the ability of EGCg to modulate macrophage immune functions in an in vitro Legionella pneumophila infection model of macrophages was examined. The study showed that EGCg inhibited the growth of L. pneumophila in macrophages at a concentration as low as 0.5 mug/ml without any direct antibacterial effect on the organisms. The EGCg selectively upregulated the production of interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-alpha) and downregulated IL-10 production of macrophages induced by L. pneumophila infection in a dose-dependent manner, but did not alter IL-6 production even at a high dose. The upregulation of the levels of macrophage gamma interferon (IFN-gamma) mRNA by EGCg was also demonstrated. Treatment of macrophage cultures with anti-TNF-a and anti-IFN-gamma monoclonal antibodies markedly abolished the anti-L. pneumophila activity of macrophages induced by the EGCg treatment. These results indicate that EGCg selectively alters the immune responses of macrophages to L. pneumophila and leads to an enhanced anti-L. pneumophila activity of macrophages mediated by enhanced production of both TNF-alpha and IFN-gamma. However, the enhancement of in vitro anti-L. pneumophila activity by EGCg may not be directly mediated by IL-10 and IL-12 production modulation. Thus, the results of this study revealed the immunomodulatory effect of EGCg on macrophages, which have a critical role in infections.