Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, Chaoyang, China.
Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, Beijing, Chaoyang, China.
Bioengineered. 2022 Jun;13(6):14329-14338. doi: 10.1080/21655979.2022.2084273.
This study aimed to investigate the expression of autophagy-related proteins in a mouse model of neuromyelitis optica (NMO). Mice were assigned to one of four groups: an animal experimental model group (NMO-EAE group, given with exogenous IL-17A), Interleukin-17 monoclonal antibody intervention group (NMO-EAE_0IL17inb), No exogenous interleukin-17 enhanced immune intervention group (NMO-EAE_0IL17), and a control group. Behavioral scores were assessed in each group, and the protein expressions of sequestosome 1 (P62), Beclin-1, the mammalian target of rapamycin (mTOR), phosphoinositide 3-kinase (PI3K-I), and LC3II/LC3I were detected using Western blotting. In the NMO-EAE_0IL17 group, the expression of Beclin-1 decreased, the LC3II/LC3I ratio was lower, and the expressions of P62, mTOR, and PI3K-I increased; after administration of IL-17A inhibitor into the brain tissue, however, the expression of Beclin-1 increased significantly, along with the LC3II/LC3I ratio, while the expressions of P62, mTOR and PI3K-I protein decreased significantly. In terms of behavioral scores, the scores of optic neuritis and myelitis were more serious, onset occurred earlier and the progress was faster, after the administration of IL-17A. In the mechanism of NMO animal model, IL-17A may regulate autophagy and affect the disease process through the activation of the PI3K-mTOR signaling pathway.
本研究旨在探讨视神经脊髓炎(NMO)小鼠模型中自噬相关蛋白的表达。将小鼠分为四组:动物实验模型组(NMO-EAE 组,给予外源性 IL-17A)、白细胞介素 17 单克隆抗体干预组(NMO-EAE_0IL17inb)、无外源性白细胞介素 17 增强免疫干预组(NMO-EAE_0IL17)和对照组。对每组的行为评分进行评估,并通过 Western blot 检测自噬相关蛋白 1(P62)、Beclin-1、哺乳动物雷帕霉素靶蛋白(mTOR)、磷酸肌醇 3-激酶(PI3K-I)和 LC3II/LC3I 的蛋白表达。在 NMO-EAE_0IL17 组,Beclin-1 的表达减少,LC3II/LC3I 比值降低,P62、mTOR 和 PI3K-I 的表达增加;然而,在脑内给予 IL-17A 抑制剂后,Beclin-1 的表达显著增加,LC3II/LC3I 比值也增加,而 P62、mTOR 和 PI3K-I 蛋白的表达则显著降低。在行为评分方面,IL-17A 给药后视神经炎和脊髓炎的评分更严重,发病更早,进展更快。在 NMO 动物模型的发病机制中,IL-17A 可能通过激活 PI3K-mTOR 信号通路来调节自噬并影响疾病进程。