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雷公藤甲素通过下调Th1型反应对实验性自身免疫性葡萄膜视网膜炎的抑制作用。

The suppressive effect of triptolide on experimental autoimmune uveoretinitis by down-regulating Th1-type response.

作者信息

Wu Yadi, Wang Yanping, Zhong Cuiping, Li Yuanchao, Li Xiaoyu, Sun Bing

机构信息

The Laboratory of Molecular Immunology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, PR China.

出版信息

Int Immunopharmacol. 2003 Oct;3(10-11):1457-65. doi: 10.1016/S1567-5769(03)00144-9.

Abstract

We investigated the suppressive effect of triptolide (TRD), a purified component from a traditional Chinese herb, Tripterygium wilfordii Hook F. (TWHf), on uveitogenic peptide (K2)-induced experimental autoimmune uveoretinitis (EAU). K2-peptide immunized B10.A mice were divided into four groups. One group was EAU control which was treated with PBS. The other two groups were treated with TRD with different time courses (from day 0 to day 28 and from day 14 to day 28). The last group was treated with Cyclosporin A (CsA) as a positive control of the treatment. TRD was administered at dose of 0.1 mg/kg/day (i.p.). CsA was administered at dose of 20 mg/kg/day (i.p.) from day 0 to day 28 during whole period of EAU induction. The data showed that the EAU was suppressed in the whole period of TRD-treated mice, but was not in TRD-treated mice from day 14 to day 28 following immunization. The inhibition of EAU induced by TRD treatment was comparable to CsA-treated mice. The K2-specific lymphocyte proliferation and mRNA expressions of Th1-type cytokines (IL-12p40, IFN-gamma and TNF-alpha) in draining lymph node and inflamed eyes were reduced in TRD-treated mice. The K2-specific IFN-gamma production in the draining lymph node cells (LNC) of TRD-treated mice (whole period) was significantly inhibited. This effect was not related to an apoptotic effect of TRD on CD4+ T cells. Our results suggested that TRD suppressed the induction of EAU by down-regulating Th1-type response in B10.A mice. This preventive effect on EAU induction may be related to the inhibition of TRD on T cell priming and activation.

摘要

我们研究了雷公藤甲素(TRD),一种从传统中药雷公藤(Tripterygium wilfordii Hook F.,TWHf)中提取的纯化成分,对致葡萄膜炎肽(K2)诱导的实验性自身免疫性葡萄膜视网膜炎(EAU)的抑制作用。用K2肽免疫的B10.A小鼠被分为四组。一组为EAU对照组,用磷酸盐缓冲液(PBS)处理。另外两组在不同的时间疗程(从第0天至第28天和从第14天至第28天)用TRD处理。最后一组用环孢素A(CsA)作为治疗的阳性对照。TRD以0.1mg/kg/天的剂量腹腔注射给药。在EAU诱导的整个期间,从第0天至第28天,CsA以20mg/kg/天的剂量腹腔注射给药。数据显示,在整个TRD处理的小鼠期间EAU受到抑制,但在免疫后第14天至第28天接受TRD处理的小鼠中未受到抑制。TRD处理诱导的EAU抑制作用与CsA处理的小鼠相当。在TRD处理的小鼠中,引流淋巴结和发炎眼睛中K2特异性淋巴细胞增殖以及Th1型细胞因子(IL-12p40、干扰素-γ和肿瘤坏死因子-α)的mRNA表达降低。TRD处理的小鼠(整个期间)引流淋巴结细胞(LNC)中K2特异性干扰素-γ的产生受到显著抑制。这种作用与TRD对CD4 + T细胞的凋亡作用无关。我们的结果表明,TRD通过下调B10.A小鼠中的Th1型反应来抑制EAU的诱导。这种对EAU诱导的预防作用可能与TRD对T细胞启动和激活的抑制有关。

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