Biological evaluation of subglutinol a as a novel immunosuppressive agent for inflammation intervention.
Biological evaluation of subglutinol a as a novel immunosuppressive agent for inflammation intervention.
复制标题
subglutinol a作为炎症干预的新型免疫抑制剂的生物学评价。
DOI：
10.1021/ml4004809
复制
发表时间：
2014
影响因子：
4.2
通讯作者：
Li,Qi-Jing
中科院分区：
文献类型：
--
作者：
Lin,Regina;Kim,Hyoungsu;Hong,Jiyong;Li,Qi-Jing
亚谷氨醇A(1)是从雷公藤内生真菌亚谷氨酸镰刀菌中分离出来的一种免疫抑制天然产物。我们发现1在体外对激活的T细胞具有多模式免疫抑制作用：亚谷氨醇A(1)有效地阻止T细胞的增殖和存活，同时深刻地抑制由完全分化的效应细胞Th1和Th17产生的促炎干扰素γ和IL-17。我们的数据进一步表明，1可能通过加重T细胞线粒体损伤而发挥抗炎作用。此外，我们证明，在Th1驱动的迟发性超敏反应小鼠模型中，1显著减少了淋巴细胞对足垫的渗透，并改善了足垫肿胀。这些结果提示1有可能成为治疗炎症性疾病的一种新疗法。
Subglutinol A (1) is an immunosuppressive natural product isolated fromFusarium subglutinans, an endophytic fungus from the vineTripterygium wilfordii. We show that1exerts multimodal immune-suppressive effects on activated T cells in vitro: subglutinol A (1) effectively blocks T cell proliferation and survival while profoundly inhibiting pro-inflammatory IFNγ and IL-17 production by fully differentiated effector Th1 and Th17 cells. Our data further reveal that1may exert its anti-inflammatory effects by exacerbating mitochondrial damage in T cells. Additionally, we demonstrate that1significantly reduces lymphocytic infiltration into the footpad and ameliorates footpad swelling in the mouse model of Th1-driven delayed-type hypersensitivity. These results suggest the potential of1as a novel therapeutic for inflammatory diseases.