Department of Neurology, Huashan Hospital, Fudan University.
Department of Neurology, Fujian Medical University Union Hospital.
Int J Biol Sci. 2021 Jan 1;17(1):50-61. doi: 10.7150/ijbs.50041. eCollection 2021.
Eomesodermin (Eomes), a transcription factor, could suppress the Th17 cell differentiation and proliferation through directly binding to the promoter zone of the and gene, meanwhile the expression of is suppressed when c-Jun directly binds to its promoter zone. Ginkgolide K (1,10-dihydroxy-3,14-didehydroginkgolide, GK) is a diterpene lactone isolated from the leaves of Ginkgo biloba. A previous study indicated that GK could decrease the level of phospho JNK (c-Jun N-terminal kinase). Here, we reported the therapeutic potential of Ginkgolide K (GK) treatment to ameliorate experimental autoimmune encephalomyelitis (EAE) disease progression. EAE was induced in both wildtype and CD4- conditional knockout mice. GK was injected intraperitoneally. Disease severity, inflammation, and tissue damage were assessed by clinical evaluation, flow cytometry of mononuclear cells (MNCs), and histopathological evaluation. Dual-luciferase reporter assays were performed to measure Eomes transcription activity in vitro. The potency of GK (IC) was determined using JNK1 Kinase Enzyme System. We revealed that GK could ameliorate EAE disease progression by the inhibition of the Th17 cells. Further mechanism studies demonstrated that the level of phospho JNK was decreased and the level of Eomes in CD4T cells was dramatically increased. This therapeutic effect of GK was almost completely interrupted in CD4- conditional knockout mice. These results provided the therapeutic potential of GK treatment in EAE, and further suggested that Eomes expression in CD4T cells might be essential in this process.
Eomesodermin (Eomes)，一种转录因子，可通过直接结合 和 基因的启动子区抑制 Th17 细胞的分化和增殖，同时 c-Jun 直接结合其启动子区时会抑制 的表达。银杏内酯 K（1,10-二羟基-3,14-二脱氢银杏内酯，GK）是从银杏叶中分离出的二萜内酯。先前的研究表明，GK 可降低磷酸化 JNK（c-Jun N-末端激酶）的水平。在这里，我们报道了银杏内酯 K（GK）治疗改善实验性自身免疫性脑脊髓炎（EAE）疾病进展的治疗潜力。在野生型和 CD4-条件性敲除小鼠中均诱导 EAE。GK 通过腹腔注射给药。通过临床评估、单核细胞（MNC）的流式细胞术和组织病理学评估来评估疾病严重程度、炎症和组织损伤。进行双荧光素酶报告基因测定以体外测量 Eomes 转录活性。使用 JNK1 激酶酶系统确定 GK 的效力（IC）。我们揭示了 GK 通过抑制 Th17 细胞来改善 EAE 疾病进展。进一步的机制研究表明，磷酸化 JNK 的水平降低，CD4T 细胞中的 Eomes 水平显著增加。在 CD4-条件性敲除小鼠中，这种 GK 的治疗效果几乎完全中断。这些结果提供了 GK 治疗 EAE 的治疗潜力，并进一步表明 CD4T 细胞中的 Eomes 表达在此过程中可能是必不可少的。
