Dihydroartemisinin attenuated the symptoms of mice model of systemic lupus erythematosus by restoring the Treg/Th17 balance
Dihydroartemisinin attenuated the symptoms of mice model of systemic lupus erythematosus by restoring the Treg/Th17 balance
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DOI：
10.1111/1440-1681.13461
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发表时间：
2021-01-19
影响因子：
2.9
通讯作者：
Cha, Xushan
中科院分区：
文献类型：
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作者：
Chen, Yan;Tao, Tingjun;Cha, Xushan
Treg/th17不平衡与系统性红斑狼疮（SLE）的发展有关。二羟基甲蛋白（DHA）是阿甲米共半蛋白的半合成衍生物，与传统的中含中中的草药hartemisia annua arnua annua annua annua L.分离出来。本研究旨在评估DHA单独或在SLE免疫缺陷中与泼尼松的泼尼松。在体内，在Pristane诱导的SLE小鼠模型中评估了单独或与泼尼松结合的DHA的治疗效果。然后，血清抗体，肌酐（CRE），血尿素氮（BUN），尿液蛋白，肾脏组织病理学，白介素（IL）-17，IL-6，转化生长因子（TGF）-beta，ROR的表达，ROR的表达分析了伽马T和FOXP3，外周血和脾脏中Treg和Th17的百分比被分析。在体外，将小鼠脾淋巴细胞分离并单独用DHA或与泼尼松结合使用DHA。然后分析了Treg和Th17的百分比，IL-17，IL-6，TGF-beta的浓度以及ROR伽马T和FOXP3的表达。结果表明，单独或与泼尼松治疗结合使用DHA可显着缓解丙烷引起的SLE小鼠的表现，抑制炎症并恢复Treg/Th17平衡。 DHA单独或与泼尼松结合使用显着抑制Th17细胞分化，而在体外诱导Treg细胞分化。单独或与泼尼松结合使用DHA还降低了淋巴细胞中RORγT的转录，并增加了FOXP3，以及IL-17和TGF-β水平。我们的数据表明，DHA可以通过恢复Treg/Th17平衡来减轻SLE的症状，从而产生协同作用。
The Treg/Th17 imbalance is associated with the development of systemic lupus erythematosus (SLE). Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, is isolated from the traditional Chinese herb Artemisia annua Artemisia annua L. This study aims to evaluate the effects of DHA alone or in combination with prednisone in immunodeficiency of SLE. In vivo, the therapeutical effect of DHA alone or in combination with prednisone was assessed in the pristane-induced SLE mouse model. Then, the level of serum antibodies, creatinine (Cre), blood urea nitrogen (BUN), urine protein, kidney histopathology, interleukin (IL)-17, IL-6, transforming growth factor (TGF)-beta, the expression of ROR gamma t and Foxp3, the percentages of Treg and Th17 in peripheral blood and spleen were assayed. In vitro, the mouse spleen lymphocytes were separated and treated with DHA alone or DHA in combination with prednisone. Then the percentages of Treg and Th17, the concentration of IL-17, IL-6, TGF-beta, and the expression of ROR gamma t and Foxp3 were assayed. It was shown that DHA alone or in combination with prednisone treatment significantly alleviated the manifestations of pristane-induced SLE mice, suppressed inflammation and restored the Treg/Th17 balance. DHA alone or in combination with prednisone significantly inhibited Th17 cell differentiation while induced Treg cell differentiation in vitro. DHA alone or in combination with prednisone also reduced the transcription of ROR gamma t and increased Foxp3 in lymphocytes, as well as IL-17 and TGF-beta levels. Our data indicated that DHA can produce synergistic effect with prednisone to attenuate the symptoms of SLE by restoring Treg/Th17 balance.