Hubei Key Laboratory of Natural Medicinal Chemistry and Resources Evaluation, School of Pharmacy, Tongji Medical College, HuaZhong University of Science and Technology, Wuhan, China.
J Ethnopharmacol. 2009 Oct 29;126(1):57-63. doi: 10.1016/j.jep.2009.08.011. Epub 2009 Aug 19.
To investigate the immunosuppressive effects of HPLC qualitied ethyl acetate extract (EAE) from Urtica dentate Hand on skin allograft rejection in a murine model.
Allo-skin transplantation model was established by placing skin allograft of C57BL/6 mice in the wound bed which was on the back of Balb/c mice. We used FACS to study the effects of EAE on dendritic cells (DCs) maturation and CD4(+)CD25(+)T regulatory cells (Tregs) differentiation. We also studied spleen lymphocyte proliferation and T-bet gene expression in DCs. Concentration of Th1/Th2 cytokines was monitored as markers of Th1/Th2 responses by ELISA.
A significant prolongation of skin allografts survival was observed as a dose-dependent manner in the animals treated with EAE. By FACS, we found that treatment with EAE (200 mg kg(-1)) resulted in an immature statement of DCs and stimulated the differentiation of CD4(+)CD25(+)Tregs. Additionally, the expression of T-bet gene and the proliferation of spleen lymphocytes were efficiently abated in EAE treated mice. Comparing to the model control, EAE-treated recipients showed a significant down-regulation (P<0.01) of Th1 cytokines (IL-2, IFN-gamma) and an obviously increase (P<0.01) of Th2 cytokine (IL-10) in the serum, which presented in a dose-related way.
The anti-allograft rejection effect of EAE by enhancing CD4(+)CD25(+)Tregs differentiation and sustaining DCs immaturation makes EAE to be a possible choice for treating autoimmune diseases in a way of inducing a stable immunological tolerance state.
研究小刺荨麻乙酸乙酯提取物（EAE）对小鼠皮肤同种异体移植排斥的免疫抑制作用。
通过将 C57BL/6 小鼠的皮肤移植物置于 Balb/c 小鼠背部的创伤床上，建立同种异体皮肤移植模型。我们使用 FACS 研究 EAE 对树突状细胞（DCs）成熟和 CD4+CD25+调节性 T 细胞（Tregs）分化的影响。我们还研究了脾淋巴细胞增殖和 DCs 中的 T-bet 基因表达。通过 ELISA 监测 Th1/Th2 细胞因子的浓度作为 Th1/Th2 反应的标志物。
在 EAE 治疗的动物中，观察到皮肤移植物存活时间显著延长，呈剂量依赖性。通过 FACS，我们发现 EAE（200mg/kg）处理导致 DCs 的不成熟状态，并刺激 CD4+CD25+Tregs 的分化。此外，EAE 处理的小鼠中 T-bet 基因的表达和脾淋巴细胞的增殖均被有效抑制。与模型对照组相比，EAE 治疗的受者血清中 Th1 细胞因子（IL-2、IFN-γ）明显下调（P<0.01），Th2 细胞因子（IL-10）明显增加（P<0.01），呈剂量依赖性。
EAE 通过增强 CD4+CD25+Tregs 的分化和维持 DCs 的未成熟状态来抑制移植物排斥反应，使其成为诱导稳定免疫耐受状态以治疗自身免疫性疾病的一种可能选择。
