9,10-Anhydrodehydroartemisinin Attenuates Experimental Autoimmune Encephalomyelitis by Inhibiting Th1 and Th17 Cell Differentiation
9,10-Anhydrodehydroartemisinin Attenuates Experimental Autoimmune Encephalomyelitis by Inhibiting Th1 and Th17 Cell Differentiation
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9,10-AnHydrodehydroartemisinin 通过抑制 Th1 和 Th17 细胞分化来减轻实验性自身免疫性脑脊髓炎。
DOI：
10.1007/s10753-021-01456-5
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发表时间：
2021-03-31
期刊：
影响因子：
5.1
通讯作者：
Du, Changsheng
中科院分区：
文献类型：
--
作者：
Lv, Jie;Zhuang, Wei;Du, Changsheng
多发性硬化（multiple sclerosis，MS）是一种中枢神经系统（central nervous system，CNS）脱髓鞘疾病。实验性自身免疫性脑脊髓炎（experimental autoimmune encephalomyelitis，EAE）是最常用的实验模型，其主要病理特征与多发性硬化（MS）相似。然而，MS没有治愈方法，MS的治疗仍然面临巨大挑战。因此，寻找更有效的疾病缓解治疗迫在眉睫。在本研究中，我们研究了青蒿素衍生物9，10-脱水脱氢青蒿素（ADART）是否可以减少EAE的脱髓鞘及其潜在机制。在已建立的EAE小鼠中，100 mg/kg 9，10-脱水脱氢青蒿素（ADART）可有效减少CNS和外周免疫系统浸润炎性细胞，包括CD 4（+）IFN-γ（+）Th 1细胞和CD 4（+）IL-17 A（+）Th 17细胞。相应地，IFN-γ和IL-17 A的血清水平也降低。在体外，ADART在10 μ M时几乎完全抑制Th 17分化，部分抑制Th 1分化。这项研究表明，ADART可能是目前MS治疗中一个很有前途的途径。
Human inflammatory disease, multiple sclerosis (MS), is a demyelinating disease of central nervous system (CNS). The experimental autoimmune encephalomyelitis (EAE) is the most commonly used as experimental model because of its key pathological features' approximation of MS. The interaction between complex elements in immune system and in the CNS determines the MS pathogenesis. However, there is no cure for MS and the treatment for MS still encounters great challenges. Thus, finding a more effective disease-modifying treatment is imminent. In the present study, we investigated whether 9,10-Anhydrodehydroartemisin (ADART), a compound derived from artemisinin, could decrease demyelination in EAE and the underlying mechanisms. In established EAE mice, 100 mg/kg 9,10-Anhydrodehydroartemisinin (ADART) effectively reduced CNS and peripheral immune system infiltration inflammatory cells including CD4(+) IFN-gamma(+) Th1 cells and CD4(+) IL-17A(+) Th17 cells. Correspondingly, the serum level of IFN-gamma and IL-17A was also reduced. In vitro, ADART almost completely inhibited Th17 differentiation, and partially inhibited Th1 differentiation in 10 mu M. This research revealed that ADART could be a great promising avenue among current therapies for MS.