SM934, a water-soluble derivative of arteminisin, exerts immunosuppressive functions in vitro and in vivo
SM934, a water-soluble derivative of arteminisin, exerts immunosuppressive functions in vitro and in vivo
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DOI：
10.1016/j.intimp.2009.09.003
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发表时间：
2009-12-01
影响因子：
5.6
通讯作者：
Zuo, Jian-Ping
中科院分区：
文献类型：
--
作者：
Hou, Li-Fei;He, Shi-Jun;Zuo, Jian-Ping
本研究探讨了青蒿素衍生物马来酸氨基青蒿醚（SM 934）对T细胞活化的免疫抑制作用及其机制。在体外，SM 934可显著抑制刀豆球蛋白A（ConA）、脂多糖（LPS）、混合淋巴细胞反应（MLR）和抗CD 3/抗CD 28（anti-CD 3/28）诱导的脾细胞增殖。SM 934显著抑制干扰素（IFN）-γ的产生和抗CD 3/28刺激的CD 4（+）T细胞分裂。SM 934还促进抗CD 3/28刺激的CD 4（+）T细胞中CD 69（+）群体的凋亡。此外，SM 934通过阻断活化T细胞中Akt磷酸化来抑制白细胞介素（IL）-2介导的增殖和存活。在卵清蛋白（OVA）免疫小鼠中，口服SM 934抑制OVA特异性T细胞增殖和IFN-γ产生。SM 934处理还显著抑制绵羊红细胞（SRBC）诱导的小鼠迟发型超敏反应（DTH）。综上所述，SM 934在体外和体内均显示出有效的免疫抑制活性。我们的研究结果表明，SM 934可能是一种潜在的免疫相关疾病的治疗药物。(C)2009 Elsevier B. V.保留所有权利。
In the present study, we investigated the immunosuppressive effects and underlying mechanisms of aminoarteether maleate (SM934), a derivative of artemisinin, against T cell activation in vitro and in vivo. In vitro, SM934 significantly inhibited the proliferation of splenocytes induced by concanavalin A (Con A), lipopolysaccharide (LPS), mixed lymphocyte reaction (MLR), and anti-CD3 plus anti-CD28 (anti-CD3/28). SM934 significantly inhibited interferon (IFN)-gamma production and CD4(+) T cell division stimulated by anti-CD3/28. SM934 also promoted apoptosis of CD69(+) population in CD4(+) T cells stimulated by anti-CD3/28. Furthermore, SM934 inhibited interleukin (IL)-2 mediated proliferation and survival through blocking Akt phosphorylation in activated T cells. In ovalbumin (OVA)-immunized mice, oral administration of SM934 suppressed OVA-specific T cell proliferation and IFN-gamma production. SM934 treatment also significantly inhibited the sheep red blood cell (SRBC)-induced delayed type hypersensitivity (DTH) reactions in mice. Taken together, SM934 showed potent immunosuppressive activities in vitro and in vivo. Our results demonstrated that SM934 might be a potential therapeutic agent for immune-related diseases. (C) 2009 Elsevier B.V. All rights reserved.