NAD+ 通过诱导 CD11b+gr-1+ 髓系来源的抑制性细胞来减轻实验性自身免疫性脑脊髓炎。
NAD+ attenuates experimental autoimmune encephalomyelitis through induction of CD11b+ gr-1+ myeloid-derived suppressor cells.
机构信息
Department of Neurology, The Second Hospital of Hebei Medical University, Key Laboratory of Hebei Neurology, No. 215 Heping Road, Shijiazhuang 050000, Hebei, China.
出版信息
Biosci Rep. 2020 Apr 30;40(4). doi: 10.1042/BSR20200353.
OBJECTIVE
To investigate the effects of nicotinamide adenine dinucleotide (NAD+) on the pathogenesis of the animal model for multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE).
METHODS
EAE model was induced by myelin oligodendrocyte protein (MOG 35-55). Clinical scores of EAE were measured in mice with or without NAD+ treatment. Hematoxylin and Eosin (HE) and Luxol Fast Blue (LFB) staining were performed to assess inflammation and demyelination, respectively. Expressions of target proteins were measured by Western blot. The numbers of myeloid-derived suppressor cells (MDSCs) were measured by immunofluorescent staining and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to measure the expressions of inflammatory cytokine in serum.
RESULTS
NAD+ treatment could decrease inflammatory cells and demyelination foci, attenuate the clinical scores of EAE and slightly delay disease onset. Western blot showed that NAD+ treatment up-regulated the expression of phosphorylated-STAT6 (p-STAT6) and SIRT1. Besides, NAD+ treatment up-regulated the expression of p-IκB and down-regulated the expression of p-NF-κB. In addition, NAD+ treatment could increase the numbers of CD11b+ gr-1+ MDSCs and the expression of Arginase-1. Moreover, NAD+ treatment up-regulated the expressions of IL-13 and down-regulated the expression of IFN-γ and IL-17.
CONCLUSIONS
The present study demonstrated that NAD+ treatment may induce the CD11b+ gr-1+ MDSCs to attenuate EAE via activating the phosphorylation of STAT6 expression. Therefore, NAD+ should be considered as a potential novel therapeutic strategy for MS.
目的
研究烟酰胺腺嘌呤二核苷酸（NAD+）对多发性硬化症（MS）-实验性自身免疫性脑脊髓炎（EAE）动物模型发病机制的影响。
方法
通过髓鞘少突胶质细胞糖蛋白（MOG 35-55）诱导 EAE 模型。在给予或不给予 NAD+治疗的情况下，测量 EAE 小鼠的临床评分。通过苏木精和伊红（HE）和卢索快速蓝（LFB）染色分别评估炎症和脱髓鞘情况。通过 Western blot 测量靶蛋白的表达。通过免疫荧光染色和流式细胞术测量髓样来源的抑制细胞（MDSCs）的数量。酶联免疫吸附试验（ELISA）用于测量血清中炎症细胞因子的表达。
结果
NAD+治疗可减少炎症细胞和脱髓鞘病灶，减轻 EAE 的临床评分并轻度延迟疾病发作。Western blot 显示 NAD+治疗可上调磷酸化-STAT6（p-STAT6）和 SIRT1 的表达。此外，NAD+治疗可上调 p-IκB 的表达并下调 p-NF-κB 的表达。此外，NAD+治疗可增加 CD11b+gr-1+MDSCs 的数量并上调精氨酸酶-1的表达。此外，NAD+治疗可上调 IL-13 的表达并下调 IFN-γ和 IL-17 的表达。
结论
本研究表明，NAD+治疗可能通过激活 STAT6 表达的磷酸化诱导 CD11b+gr-1+MDSCs 减轻 EAE。因此，NAD+可被视为治疗 MS 的一种有前途的新策略。
Zotero 插件