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Jaceosidin 通过下调 T 细胞中的 IFN-γ/STAT1/T-bet 信号通路抑制小鼠接触性超敏反应。

Jaceosidin inhibits contact hypersensitivity in mice via down-regulating IFN-γ/STAT1/T-bet signaling in T cells.

机构信息

School of Life Sciences, Nanjing University, Nanjing 210093, China.

出版信息

Eur J Pharmacol. 2011 Jan 25;651(1-3):205-11. doi: 10.1016/j.ejphar.2010.10.068. Epub 2010 Nov 18.

Abstract

In the present study, we aimed to investigate the immunosuppressive activity of jaceosidin, a flavone isolated from Artemisia vestita, on T lymphocytes both in vitro and in vivo, and further explore its potential molecular mechanism. Jaceosidin exerted a significant inhibition on the T cell proliferation and activation induced by concanavalin A (Con A) in a concentration-dependent manner and it also inhibited the secretion of the proinflammatory cytokines such as IL-2, TNF-α and IFN-γ of activated T cells. Further study showed that jaceosidin down-regulated STAT1 activation and T-bet expression in activated T cells. Moreover, in order to investigate the immunosuppressive effect of jaceosidin in vivo, the picryl chloride (PCl)-induced ear contact dermatitis model was performed on BALB/c mice. Jaceosidin significantly ameliorated PCl-induced ear swelling in a dose-dependent manner, which was due to its inhibition of the STAT1/T-bet signaling pathway. In summary, these findings suggest that jaceosidin exerts its immunosuppressive effect both in vitro and in vivo through inhibiting T cell proliferation and activation, which is closely associated with its potent down-regulation of the IFN-γ/STAT1/T-bet signaling pathway.

摘要

在本研究中,我们旨在研究从艾蒿中分离出的类黄酮芹菜素在体外和体内对 T 淋巴细胞的免疫抑制活性,并进一步探讨其潜在的分子机制。芹菜素以浓度依赖的方式显著抑制刀豆蛋白 A(Con A)诱导的 T 细胞增殖和活化,并抑制活化 T 细胞中促炎细胞因子如 IL-2、TNF-α和 IFN-γ的分泌。进一步的研究表明,芹菜素下调了活化 T 细胞中 STAT1 的激活和 T-bet 的表达。此外,为了研究芹菜素在体内的免疫抑制作用,我们在 BALB/c 小鼠上进行了对二硝基氯苯(PCl)诱导的耳部接触性皮炎模型的研究。芹菜素以剂量依赖的方式显著改善 PCl 诱导的耳部肿胀,这归因于其对 STAT1/T-bet 信号通路的抑制。综上所述,这些发现表明,芹菜素通过抑制 T 细胞增殖和活化在体内外发挥其免疫抑制作用,这与其对 IFN-γ/STAT1/T-bet 信号通路的强效下调密切相关。

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