Xie Li, Chen Jing, McMickle Anthony, Awar Nadia, Nady Soad, Sredni Benjamin, Drew Paul D, Yu Shiguang
Arkansas Biosciences Institute, Department of Biological Sciences, Arkansas State University, Jonesboro, AR 72467, USA; Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, 250117, Shandong Province, China.
Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
J Neuroimmunol. 2014 Aug 15;273(1-2):31-41. doi: 10.1016/j.jneuroim.2014.05.015. Epub 2014 Jun 7.
We reported that AS101 (organotellurium compound, trichloro(dioxoethylene-O,O') tellurate) inhibited the differentiation of Th17 cells and reduced the production of IL-17 and GM-CSF. In addition, AS101 promoted the production of IL-2 in activated T cells. Flow cytometric analysis showed that AS101 inhibited Th17 cell proliferation. AS101 blocked the activation of transcriptional factor NFAT, Stat3, and RORγt, and increased activation of Erk1/2, suggesting a mechanism of action of AS101. We further demonstrated that AS101 was effective in amelioration of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Finally, by real-time PCR analysis we showed that AS101 reduces the IL-17, IFN-γ, GM-CSF, and IL-6 mRNA expression in inflammatory cells of spinal cords. Additionally, flow cytometry analysis also indicated that the CD4+ T cells and IL-17 and GM-CSF-producing cells were reduced in the spinal cords of AS101 treated mice compared to those treated with PBS.
我们报道了AS101（有机碲化合物，三氯（二氧乙烯-O,O'）碲酸盐）可抑制Th17细胞的分化，并减少白细胞介素-17（IL-17）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）的产生。此外，AS101可促进活化T细胞中白细胞介素-2（IL-2）的产生。流式细胞术分析表明，AS101可抑制Th17细胞增殖。AS101可阻断转录因子活化T细胞核因子（NFAT）、信号转导和转录激活因子3（Stat3）以及维甲酸相关孤儿受体γt（RORγt）的活化，并增强细胞外信号调节激酶1/2（Erk1/2）的活化，提示了AS101的作用机制。我们进一步证明，AS101对实验性自身免疫性脑脊髓炎（EAE，一种多发性硬化症的动物模型）具有改善作用。最后，通过实时聚合酶链反应（PCR）分析，我们发现AS101可降低脊髓炎症细胞中IL-17、干扰素-γ（IFN-γ）、GM-CSF和IL-6的信使核糖核酸（mRNA）表达。此外，流式细胞术分析还表明，与用磷酸盐缓冲液（PBS）处理的小鼠相比，经AS101处理的小鼠脊髓中CD4+T细胞以及产生IL-17和GM-CSF的细胞数量减少。
