Department of Paediatrics, First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Internal Medicine, Medical College of Nanchang University, Nanchang, China.
Clin Exp Pharmacol Physiol. 2021 Mar;48(3):329-336. doi: 10.1111/1440-1681.13434. Epub 2020 Nov 20.
The pathogenesis of systemic lupus erythematosus (SLE) is closely associated with aberrant immune system. Here, the aim of our study was to explore the regulation of cucurbitacin IIb (CuIIb) to Th17/Treg cells in SLE. Compared with normal mice, the percentage of Treg cells was downregulated in SLE mouse model, and Th17 was upregulated. Meantime, the production of Treg-related transcription factor (foxp3) in SLE model mouse was reduced, and the production of Th17-related transcription factor (RORγt) was increased. After treatment with CuIIb, the percentage of Treg cells in SLE mice was partly upregulated, and Th17 cells percentage was downregulated. The expression of foxp3 and RORγt in SLE mice were promoted and inhibited by CuIIb treatment, respectively. SLE-induced kidney injury also was improved by CuIIb treatment. In vitro, we demonstrated again that CuIIb upregulated the percentage of Treg cells in lymphocytes from SLE mice, and downregulated the percentage of Th17 cells. Highly expressed IL-6 and IL17, and lowly expressed IL-10 and TGF-β in lymphocytes from SLE mice were repressed and facilitated by CuIIb treatment, respectively. Overall, our data proved that CuIIb improved kidney injury in SLE mice through balancing the percentage of Th17 and Treg cells. Our data provided a reliable evidence to support the potential of CuIIb in SLE treatment.
系统性红斑狼疮(SLE)的发病机制与免疫系统异常密切相关。本研究旨在探讨葫芦素 IIb(CuIIb)对 SLE 中 Th17/Treg 细胞的调控作用。与正常小鼠相比,SLE 小鼠模型中 Treg 细胞的比例下调,而 Th17 细胞上调。同时,SLE 模型小鼠中 Treg 相关转录因子(foxp3)的产生减少,而 Th17 相关转录因子(RORγt)的产生增加。用 CuIIb 治疗后,SLE 小鼠 Treg 细胞的比例部分上调,Th17 细胞的比例下调。CuIIb 处理分别促进和抑制 SLE 小鼠中 foxp3 和 RORγt 的表达。CuIIb 治疗还改善了 SLE 诱导的肾脏损伤。在体外,我们再次证明 CuIIb 上调了来自 SLE 小鼠淋巴细胞中 Treg 细胞的比例,下调了 Th17 细胞的比例。CuIIb 处理分别抑制和促进了来自 SLE 小鼠淋巴细胞中高表达的 IL-6 和 IL17,以及低表达的 IL-10 和 TGF-β。
综上所述,我们的数据证明 CuIIb 通过平衡 Th17 和 Treg 细胞的比例改善了 SLE 小鼠的肾脏损伤。我们的数据为支持 CuIIb 在 SLE 治疗中的潜力提供了可靠的证据。