The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul, South Korea;
Division of Rheumatology, Department of Internal Medicine, Hallym University Kang-Nam Sacred Heart Hospital, Seoul, Korea.
J Leukoc Biol. 2016 Sep;100(3):559-68. doi: 10.1189/jlb.3A0514-261RR. Epub 2016 Mar 8.
The green tea polyphenol epigallocatechin-3-gallate is a potent antioxidant. Here, we describe the effects of epigallocatechin-3-gallate on T cell differentiation and osteoclast differentiation in an animal model of arthritis. Mice with collagen-induced arthritis were injected intraperitoneally with epigallocatechin-3-gallate, 3 times/wk after the primary immunization. Surface markers of T helper 17 cells and regulatory T cells were analyzed by flow cytometry. Flow cytometry, Western blotting, and enzyme-linked immunosorbent assays were used to evaluate the effect of epigallocatechin-3-gallate on cell signaling in the collagen-induced arthritis model. Epigallocatechin-3-gallate decreased the arthritis index and showed protective effects against joint destruction in collagen-induced arthritis mice. The expression of cytokines, oxidative stress proteins, and phosphorylated-signal transducer and activator of transcription-3, 705 and 727, were significantly less in mice treated with epigallocatechin-3-gallate than it was in controls. Epigallocatechin-3-gallate reduced the expression of osteoclast markers in vitro and in vivo relative to the control, and the antiosteoclastic activity was observed in epigallocatechin-3-gallate-treated, interferon-γ knockout mice. The proportion of forkhead box protein 3-positive regulatory T cells was increased in the spleens of mice treated with epigallocatechin-3-gallate compared with control mice, whereas the proportion of T helper 17 cells was reduced. In vitro, the expression of nuclear respiratory factor 2, heme oxygenase-1, and extracellular signal-regulated kinase was increased significantly by epigallocatechin-3-gallate. We demonstrated that the administration of epigallocatechin-3-gallate attenuated the symptoms of arthritis, inhibited osteoclastogenesis and T helper 17 cell activation, and increased the number of regulatory T cells. At the molecular level, the antiarthritic effects of epigallocatechin-3-gallate may be due to induction of phosphorylated-extracellular signal-regulated kinase, nuclear respiratory factor 2, and heme oxygenase-1 and inhibition of signal transducer and activator of transcription-3 activation.
绿茶多酚表没食子儿茶素没食子酸酯是一种有效的抗氧化剂。在这里，我们描述了表没食子儿茶素没食子酸酯在关节炎动物模型中对 T 细胞分化和破骨细胞分化的影响。在初次免疫后，每周三次给胶原诱导性关节炎小鼠腹腔内注射表没食子儿茶素没食子酸酯。通过流式细胞术分析 T 辅助 17 细胞和调节性 T 细胞的表面标记物。流式细胞术、Western blot 和酶联免疫吸附试验用于评估表没食子儿茶素没食子酸酯对胶原诱导性关节炎模型中细胞信号转导的影响。表没食子儿茶素没食子酸酯降低关节炎指数，并显示对胶原诱导性关节炎小鼠关节破坏的保护作用。与对照组相比，用表没食子儿茶素没食子酸酯处理的小鼠中细胞因子、氧化应激蛋白和磷酸化信号转导和转录激活因子 3、705 和 727 的表达明显减少。表没食子儿茶素没食子酸酯减少了体外和体内破骨细胞标志物的表达，并且在干扰素-γ 敲除小鼠中观察到抗破骨细胞活性。与对照组相比，用表没食子儿茶素没食子酸酯处理的小鼠脾脏中叉头框蛋白 3 阳性调节性 T 细胞的比例增加，而 T 辅助 17 细胞的比例减少。体外，表没食子儿茶素没食子酸酯显著增加核呼吸因子 2、血红素加氧酶-1 和细胞外信号调节激酶的表达。我们证明，表没食子儿茶素没食子酸酯的给药减轻了关节炎的症状，抑制了破骨细胞生成和 T 辅助 17 细胞的激活，并增加了调节性 T 细胞的数量。在分子水平上，表没食子儿茶素没食子酸酯的抗关节炎作用可能是由于诱导磷酸化细胞外信号调节激酶、核呼吸因子 2 和血红素加氧酶-1 以及抑制信号转导和转录激活因子 3 激活。
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