Ge Z-Z, Wu Y-B, Xue Z-Y, Zhang K, Zhang R-X
Department of Geriatrics, Aviation General Hospital, Beijing, China.
Department of Neurology, Aviation General Hospital, Beijing, China.
J Physiol Pharmacol. 2021 Apr;72(2). doi: 10.26402/jpp.2021.2.05. Epub 2021 Aug 6.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). There is currently no satisfactory treatment for this disease. Pin1 is the only known peptidyl-prolyl cis/trans isomerase (PPIase) that is involved in many cellular processes, including immune responses. Numerous studies have shown that juglone effectively inhibits Pin1 activity. However, the effect of Pin1 inhibitor juglone on autoimmune diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), remain incomplete. So the present study aimed to explore the therapeutic effects of the Pin1 inhibitor juglone on EAE. EAE was induced in C57BL/6 mice with myelin oligodendrocyte glycoprotein (MOG) and treatment with juglone. The health status of EAE was observed and inflammation explored using pathological analysis. The impact of juglone on immune cells was further examined using intracellular staining and flow cytometry. The results demonstrated that juglone ameliorates EAE and reduces inflammation and demyelination in the CNS. The study also found that juglone suppresses pathogenic Th1 and Th17 cells and the expression of CD83 and MHCII on dendritic cells in EAE. In addition, juglone ameliorates EAE. Pin1 inhibitors therefore hold great promise for autoimmune disease and MS therapy.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性炎症性脱髓鞘疾病。目前尚无针对该疾病的令人满意的治疗方法。Pin1是唯一已知的肽基脯氨酰顺/反异构酶（PPIase），它参与包括免疫反应在内的许多细胞过程。大量研究表明胡桃醌可有效抑制Pin1活性。然而，Pin1抑制剂胡桃醌对自身免疫性疾病如多发性硬化症（MS）及其动物模型实验性自身免疫性脑脊髓炎（EAE）的影响仍不明确。因此，本研究旨在探讨Pin1抑制剂胡桃醌对EAE的治疗作用。用髓鞘少突胶质细胞糖蛋白（MOG）诱导C57BL/6小鼠发生EAE，并给予胡桃醌治疗。观察EAE的健康状况，并通过病理分析探究炎症情况。使用细胞内染色和流式细胞术进一步检测胡桃醌对免疫细胞的影响。结果表明，胡桃醌可改善EAE，并减轻中枢神经系统的炎症和脱髓鞘。该研究还发现，胡桃醌可抑制致病性Th1和Th17细胞以及EAE中树突状细胞上CD83和MHCII的表达。此外，胡桃醌可改善EAE。因此，Pin1抑制剂在自身免疫性疾病和MS治疗方面具有很大的前景。
