School of Pharmacy, Anhui Medical University, Hefei 230032, China.
Can J Physiol Pharmacol. 2010 Jan;88(1):45-53. doi: 10.1139/Y09-094.
This study was to investigate the effect of leflunomide on the immunosuppressive CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) in collagen-induced arthritis (CIA) rats. CIA was induced by collagen type II in Wistar rats. Immunofluorescence flow cytometry and RT-PCR were used to determine the proportion of CD4+CD25+ Tregs and the expression of Foxp3 mRNA, respectively. Proliferation of T lymphocytes was assayed with MTT reagent, and the level of transforming growth factor beta1 (TGF-beta1) in the supernatant of concanavalin A (Con A)-induced T lymphocytes was determined by ELISA kit. Our investigations demonstrated that inhibition of arthritis by leflunomide was related to changes in CD4+CD25+ Tregs. In addition, A771726, which is the active metabolite of leflunomide, promoted the differentiation of spleen lymphocytes into CD4+CD25+ Tregs, increased antiinflammatory cytokine TGF-beta1 secretion, and adjusted the activity of Con A-induced lymphocytes in vitro.
本研究旨在探讨来氟米特对胶原诱导性关节炎（CIA）大鼠免疫抑制性 CD4+CD25+调节性 T 细胞（CD4+CD25+Tregs）的影响。采用 II 型胶原诱导 Wistar 大鼠 CIA。免疫荧光流式细胞术和 RT-PCR 分别用于测定 CD4+CD25+Tregs 的比例和 Foxp3 mRNA 的表达。MTT 试剂检测 T 淋巴细胞的增殖，ELISA 试剂盒检测刀豆蛋白 A（Con A）诱导的 T 淋巴细胞上清液中转化生长因子β1（TGF-β1）的水平。我们的研究表明，来氟米特抑制关节炎与 CD4+CD25+Tregs 的变化有关。此外，来氟米特的活性代谢产物 A771726 促进了脾淋巴细胞向 CD4+CD25+Tregs 的分化，增加了抗炎细胞因子 TGF-β1 的分泌，并调节了 Con A 诱导的淋巴细胞在体外的活性。
