Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, China; CAS Key Laboratory for Receptor Research, Shanghai Institute of Materia, Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
Cell Immunol. 2022 Mar;373:104500. doi: 10.1016/j.cellimm.2022.104500. Epub 2022 Mar 5.
Multiple sclerosis (MS) was one of the major conditions causing neurological dysfunction and was an incurable progressive central nervous system disease. Experimental autoimmune encephalomyelitis (EAE) was the most commonly used experimental model of MS. Artemisinin have been shown to exhibit anti-inflammatory effects through unclear mechanisms. In this study, we aimed to evaluate the effect of administration of the artemisinin derivative TPN10466 in EAE. TPN10466 alleviated the severity of disease in EAE. Further studies showed that TPN10466 inhibited lymphocyte migration by downregulating chemokine expression and adhesion molecules. In addition, studies showed that TPN10466 directly inhibited Th1 and Th17 differentiation and reduced Th1 and Th17 infiltration into the central nervous system. In conclusion, our work demonstrated that TPN10466 provided protection against the autoimmune disease EAE by inhibiting the migration of immune cells and suppressing Th1/Th17 differentiation, suggesting that TPN10466 could be a potential for promising potential agent for the treatment of MS/EAE.
多发性硬化症（MS）是导致神经功能障碍的主要疾病之一，是一种无法治愈的进行性中枢神经系统疾病。实验性自身免疫性脑脊髓炎（EAE）是最常用于 MS 的实验模型。青蒿素通过不明机制表现出抗炎作用。在这项研究中，我们旨在评估青蒿素衍生物 TPN10466 在 EAE 中的给药效果。TPN10466 缓解了 EAE 的严重程度。进一步的研究表明，TPN10466 通过下调趋化因子表达和粘附分子来抑制淋巴细胞迁移。此外，研究表明，TPN10466 直接抑制 Th1 和 Th17 分化，并减少 Th1 和 Th17 浸润中枢神经系统。总之，我们的工作表明，TPN10466 通过抑制免疫细胞的迁移和抑制 Th1/Th17 分化来提供对自身免疫性疾病 EAE 的保护，这表明 TPN10466 可能是治疗 MS/EAE 的有前途的潜在药物。
