Yakubogullari Nilgun, Cagir Ali, Bedir Erdal, Sag Duygu
Department of Bioengineering, Izmir Institute of Technology, Izmir 35430, Turkey.
Department of Chemistry, Izmir Institute of Technology, Izmir 35430, Turkey.
Vaccines (Basel). 2023 Feb 21;11(3):495. doi: 10.3390/vaccines11030495.
Astragaloside VII (AST VII), a triterpenic saponin isolated from species, shows promise as a vaccine adjuvant, as it supported a balanced Th1/Th2 immune response in previous in vivo studies. However, the underlying mechanisms of its adjuvant activity have not been defined. Here, we investigated the impact of AST VII and its newly synthesized semi-synthetic analogs on human whole blood cells, as well as on mouse bone marrow-derived dendritic cells (BMDCs). Cells were stimulated with AST VII and its derivatives in the presence or absence of LPS or PMA/ionomycin and the secretion of cytokines and the expression of activation markers were analyzed using ELISA and flow cytometry, respectively. AST VII and its analogs increased the production of IL-1β in PMA/ionomycin-stimulated human whole blood cells. In LPS-treated mouse BMDCs, AST VII increased the production of IL-1β and IL-12, and the expression of MHC II, CD86, and CD80. In mixed leukocyte reaction, AST VII and derivatives increased the expression of the activation marker CD44 on mouse CD4 and CD8 T cells. In conclusion, AST VII and its derivatives strengthen pro-inflammatory responses and support dendritic cell maturation and T cell activation in vitro. Our results provide insights into the mechanisms of the adjuvant activities of AST VII and its analogs, which will be instrumental to improve their utility as a vaccine adjuvant.
黄芪甲苷VII（AST VII）是从某物种中分离出的一种三萜皂苷，作为疫苗佐剂显示出应用前景，因为在之前的体内研究中它能支持Th1/Th2免疫反应平衡。然而，其佐剂活性的潜在机制尚未明确。在此，我们研究了AST VII及其新合成的半合成类似物对人全血细胞以及小鼠骨髓来源的树突状细胞（BMDC）的影响。在存在或不存在脂多糖（LPS）或佛波酯/离子霉素（PMA/ionomycin）的情况下，用AST VII及其衍生物刺激细胞，分别使用酶联免疫吸附测定（ELISA）和流式细胞术分析细胞因子的分泌和激活标志物的表达。AST VII及其类似物增加了PMA/ionomycin刺激的人全血细胞中白细胞介素-1β（IL-1β）的产生。在LPS处理的小鼠BMDC中，AST VII增加了IL-1β和IL-12的产生，以及主要组织相容性复合体II类分子（MHC II）、CD86和CD80的表达。在混合淋巴细胞反应中，AST VII及其衍生物增加了小鼠CD4和CD8 T细胞上激活标志物CD44的表达。总之，AST VII及其衍生物在体外增强促炎反应并支持树突状细胞成熟和T细胞激活。我们的结果为AST VII及其类似物的佐剂活性机制提供了见解，这将有助于提高它们作为疫苗佐剂的效用。
