SBF-1 inhibits contact hypersensitivity in mice through down-regulation of T-cell-mediated responses
SBF-1 inhibits contact hypersensitivity in mice through down-regulation of T-cell-mediated responses
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SBF-1 通过下调 T 细胞介导的反应抑制小鼠接触超敏反应
DOI：
10.1186/s40360-019-0377-8
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发表时间：
2019-12-21
影响因子：
2.9
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
--
作者：
Chen, Wei;Fang, Xianying;Xu, Qiang
背景T淋巴细胞在接触性超敏反应中发挥重要作用。本研究旨在探讨皂苷OSW-1类似物SBF-1在体外和体内对T淋巴细胞的免疫抑制活性。方法采用MTT法测定小鼠淋巴结T淋巴细胞增殖情况。进行流式细胞术分析以评估T细胞活化和凋亡。通过PCR和ELISA测定细胞因子的水平。用苦基氯对 BALB/c 小鼠进行致敏和攻击，并测量左右耳的厚度。结果SBF-1 在极低剂量（10nM）下能有效抑制刀豆蛋白 A（Con A）或抗 CD3 加抗 CD28 诱导的 T 淋巴细胞增殖，但在浓度高达 10μM 时对非活化 T 淋巴细胞几乎没有毒性。此外，SBF-1 抑制 Con A 激活的 T 细胞中 CD25 和 CD69 的表达以及 AKT 的磷酸化。 SBF-1 还诱导激活的 T 细胞凋亡。此外，SBF-1还以剂量依赖性方式下调T细胞细胞因子、IL-2和IFN-γ的诱导。此外，SBF-1 显着抑制苦基氯诱导的接触性超敏反应小鼠模型中的耳部肿胀和炎症。结论我们的研究结果表明，SBF-1 在体外和体内均具有独特的免疫抑制活性，主要通过抑制 T 细胞增殖和激活。其机制似乎与AKT信号通路的阻断有关。
BackgroundT lymphocytes play an important role in contact hypersensitivity. This study aims to explore the immunosuppressive activity of SBF-1, an analog of saponin OSW-1, against T lymphocytes in vitro and in vivo.MethodsProliferation of T lymphocytes from lymph nodes of mice was determined by MTT assay. Flow cytometry analysis was performed to assess T cell activation and apoptosis. Levels of cytokines were determined by PCR and ELISA. BALB/c mice were sensitized and challenged with picryl chloride and thickness of left and right ears were measured.ResultsSBF-1 effectively inhibited T lymphocytes proliferation induced by concanavalin A (Con A) or anti-CD3 plus anti-CD28 at a very low dose (10 nM) but exhibited little toxicity in non-activated T lymphocytes at concentrations up to 10 μM. In addition, SBF-1 inhibited the expression of CD25 and CD69, as well as he phosphorylation of AKT in Con A-activated T cells. SBF-1 also induced apoptosis of activated T cells. In addition, SBF-1 also downregulated the induction of the T cell cytokines, IL-2 and IFN-γ in a dose-dependent manner. Furthermore, SBF-1 significantly suppressed ear swelling and inflammation in a mouse model of picryl chloride-induced contact hypersensitivity.ConclusionsOur findings suggest that SBF-1 has an unique immunosuppressive activity both in vitro and in vivo mainly through inhibiting T cell proliferation and activation. Its mechanism appears to be related to the blockage of AKT signaling pathway.