中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (12): 2765-2770.doi: 10.4103/1673-5374.339492

• 原著:退行性病与再生 • 上一篇    下一篇

Nr4a1激动剂壳囊孢菌素B可减轻多发性硬化的神经炎症反应

  

  • 出版日期:2022-12-15 发布日期:2022-05-05
  • 基金资助:
    国家自然科学基金项目(U1804178,31870334)

NR4A1 agonist cytosporone B attenuates neuroinflammation in a mouse model of multiple sclerosis

Hai-Zhen Yu, Bing-Qing Zhu, Lin Zhu, Shuo Li, Li-Mei Wang*   

  1. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
  • Online:2022-12-15 Published:2022-05-05
  • Contact: Li-Mei Wang, MD, lylimeiwang@126.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. U1804178 (to LMW) and 31870334 (to LZ).

摘要:

Nr4a1是一种孤儿核受体,能在大多数细胞中表达,但在多发性硬化临床前阶段外周血单个核细胞中表达水平较低。此外敲除Nr4a1可加重多发性硬化的动物模型—实验性自身免疫性脑脊髓炎小鼠模型的症状。此次实验,对实验性自身免疫性脑脊髓炎小鼠模型灌胃Nr4a1受体激动剂壳囊孢菌素B。结果发现,这些小鼠表现疾病严重程度明显减轻,中枢神经系统中CD4+ T细胞和F4/80+细胞的比例和数量减少,中枢神经系统中促炎性Th1/Th17细胞和脾细胞中的细胞因子干扰素γ和白细胞介素17水平下降。表明壳囊孢菌素B可减轻实验性自身免疫性脑脊髓炎的神经损伤,因而,可作为一种治疗多发性硬化的潜在方法。

https://orcid.org/0000-0002-9566-8120 (Li-Mei Wang)

关键词: 实验性自身免疫性脑脊髓炎, Nr4a1, 激动剂, 壳囊孢菌素B, Th1, Th17, 巨噬细胞, 小胶质细胞, 多发性硬化, 治疗

Abstract: Nuclear receptor subfamily 4 group A1 (NR4A1) is an orphan nuclear receptor, which is expressed in the majority of cells. NR4A1 expression in peripheral blood mononuclear cells is low during the preclinical stage of multiple sclerosis. Knockout of the Nr4a1 gene in mice can aggravate the symptoms of experimental autoimmune encephalomyelitis (EAE), which is an animal model of multiple sclerosis. In this study, we intragastrically administered the NR4A1 agonist cytosporone B (Csn-B) to mice after inducing EAE. After treatment with Csn-B, the clinical symptoms in the EAE mice were substantially attenuated compared with that in PBS-treated control mice. The percentages of CD4+ T cells and F4/80+ cells in the central nervous system were decreased. In addition, interferon-γ and interleukin-17 production by proinflammatory Th1/Th17 cells in the central nervous system and interferon-γ levels in splenocytes were decreased after Csn-B treatment. These findings suggest that the NR4A1 agonist Csn-B can alleviate nerve injury after EAE induction, and, therefore, may be useful as a potential treatment for multiple sclerosis.

Key words: cytosporone B (Csn-B), experimental autoimmune encephalomyelitis, macrophages, microglia, multiple sclerosis, NR4A1 agonist, NR4A1, Th1, Th17, treatment