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甘草酸通过抑制C1q结合,防止视神经脊髓炎特异性IgG诱导的星形胶质细胞死亡。

Glycyrrhizic acid prevents astrocyte death by neuromyelitis optica-specific IgG via inhibition of C1q binding.

作者信息

Kim Ji-Sun, Cheon Soyoung, Kim Seung Woo, Kim Boram, Kim Heejaung, Park Ki Duk, Kim Sung-Min

机构信息

Department of Neurology, Korea University Guro Hospital, Seoul, Republic of Korea.

Department of Neurology, Seoul National University Hospital, Seoul, Republic of Korea.

出版信息

Biochem Biophys Res Commun. 2016 Sep 16;478(2):553-8. doi: 10.1016/j.bbrc.2016.07.098. Epub 2016 Jul 25.

Abstract

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system and is mediated by complement-dependent cytotoxicity (CDC) of NMO-specific immunoglobulin G (IgG) antibodies (NMO-IgG). Glycyrrhizic acid (GA) has numerous pharmacological effects including inhibition of the complement pathway. We aimed to study the influence of GA on NMO-IgG-induced CDC. NMO-IgG samples from 7 patients with NMO, together with human complement, induced CDC in an aquaporin 4 M23-overexpressing glial cell line, an in vitro NMO model. GA attenuated NMO-IgG-induced CDC in a dose-dependent manner. The mechanism of the GA-related CDC inhibition was sequentially dissected and found to involve inhibition of C1q binding to NMO-IgG. Consequently, GA attenuates NMO-IgG-induced CDC and may be a promising novel therapeutic agent against NMO.

摘要

视神经脊髓炎(NMO)是一种中枢神经系统炎性脱髓鞘疾病,由NMO特异性免疫球蛋白G(IgG)抗体(NMO-IgG)介导的补体依赖性细胞毒性(CDC)引起。甘草酸(GA)具有多种药理作用,包括抑制补体途径。我们旨在研究GA对NMO-IgG诱导的CDC的影响。来自7例NMO患者的NMO-IgG样本与人补体一起,在水通道蛋白4 M23过表达的胶质细胞系(一种体外NMO模型)中诱导CDC。GA以剂量依赖性方式减弱NMO-IgG诱导的CDC。对GA相关的CDC抑制机制进行了逐步剖析,发现其涉及抑制C1q与NMO-IgG的结合。因此,GA减弱NMO-IgG诱导的CDC,可能是一种有前景的新型抗NMO治疗药物。

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