Gong Fangyuan, Shen Yan, Zhang Chaofeng, Xu Jianliang, Wu Xuefeng, Hua Zichun, Xu Qiang
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China.
Exp Biol Med (Maywood). 2008 Sep;233(9):1124-32. doi: 10.3181/0801-RM-15. Epub 2008 Jun 5.
Activation of T cells is a critical event in the pathogenesis of concanavalin A (Con A)-induced liver injury, and facilitating apoptosis of activated T cells may provide a strategy for the treatment. Here, we found that the ethanol extract from the stem parts of Dregea volubilis (DVE) inhibited cell proliferation and induced apoptosis, which was selective for Con A-activated, rather than nonactivated, lymph node cells. Administration of DVE prevented mice from Con A-induced elevation of serum transaminases, liver necrosis and increased TNF-alpha, IFN-gamma, IL-2 and IL-4 in mice sera. DVE also caused apoptosis of in vivo activated T cells. In addition, increased active fragments of caspase-3 were found in the DVE-treated cells. But DVE-induced apoptosis was Fas-independent, as it was still observed in T cells from Fas ligand-mutated gld/gld mice. These results suggest that DVE may have great potential to treat T cell-mediated diseases through facilitating apoptosis of activated T cells.
T细胞的激活是刀豆蛋白A(Con A)诱导的肝损伤发病机制中的关键事件,促进活化T细胞的凋亡可能为治疗提供一种策略。在此,我们发现南山藤茎部的乙醇提取物(DVE)抑制细胞增殖并诱导凋亡,这对Con A活化的而非未活化的淋巴结细胞具有选择性。给予DVE可防止小鼠出现Con A诱导的血清转氨酶升高、肝坏死以及小鼠血清中TNF-α、IFN-γ、IL-2和IL-4增加。DVE还导致体内活化T细胞凋亡。此外,在DVE处理的细胞中发现caspase-3的活性片段增加。但DVE诱导的凋亡不依赖Fas,因为在Fas配体突变的gld/gld小鼠的T细胞中仍可观察到凋亡。这些结果表明,DVE可能通过促进活化T细胞凋亡在治疗T细胞介导的疾病方面具有巨大潜力。