Department of Critical Care Medicine, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing 100050, People's Republic of China.
Fitoterapia. 2012 Dec;83(8):1514-22. doi: 10.1016/j.fitote.2012.08.019. Epub 2012 Sep 5.
High mobility group box 1 protein (HMGB1), a potent pro-inflammatory cytokine, contributes to the pathogenesis of diverse inflammatory and infectious disorders. Some studies have illustrated the potential effect of HMGB1 on regulatory T cells (Tregs). Astragaloside IV (AST IV) isolated from a Chinese herb, Astragalus mongholicus, is known to have a variety of immunomodulatory activities. However, it is not yet clear whether AST IV possesses potential regulatory effect on the pro-inflammatory ability of HMGB1 with subsequent activation of Tregs. This study was carried out to investigate the antagonistic effects of different doses of AST IV on the immune function of Tregs mediated by HMGB1 in vitro. Tregs isolated from the spleens of mice were co-cultured with HMGB1 and/or AST IV. Cell phenotypes of Tregs were analyzed, and the contents of various cytokines in the cell supernatants as a result of co-culture and the proliferation of CD4(+)CD25(-) T cells were determined. Results showed that HMGB1 stimulation resulted in significantly down-regulation of expressions of Tregs cell phenotypes. However, AST IV can rival the suppressing effect of HMGB1 on immune function of Tregs with a dose-dependent in vitro. These results indicate that AST IV has the potential therapeutic action on inflammation augmented by HMGB1.
高迁移率族蛋白 B1（HMGB1）是一种强有力的促炎细胞因子，参与多种炎症和感染性疾病的发病机制。一些研究表明 HMGB1 对调节性 T 细胞（Tregs）可能具有潜在影响。从中药黄芪中分离得到的黄芪甲苷（AST IV）具有多种免疫调节作用。然而，AST IV 是否对 HMGB1 激活 Tregs 的促炎能力具有潜在的调节作用尚不清楚。本研究旨在探讨不同剂量 AST IV 对体外 HMGB1 介导的 Tregs 免疫功能的拮抗作用。从小鼠脾脏中分离的 Tregs 与 HMGB1 和/或 AST IV 共培养。分析 Tregs 的细胞表型，并测定共培养后细胞上清液中各种细胞因子的含量以及 CD4(+)CD25(-)T 细胞的增殖情况。结果表明，HMGB1 刺激导致 Tregs 细胞表型的表达明显下调。然而，AST IV 可以在体外以剂量依赖性方式拮抗 HMGB1 对 Tregs 免疫功能的抑制作用。这些结果表明 AST IV 对 HMGB1 增强的炎症具有潜在的治疗作用。
