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Silencing Leukocyte Immunoglobulin-Like Receptor A1 in Monocytes Inhibits Inflammation in Mice with Multiple Sclerosis.
Neuroimmunomodulation ( IF 2.2 ) Pub Date : 2019-01-23 , DOI: 10.1159/000495625
Shuang Zhang 1 , Xu Ma 1 , Jin Fu 2
Affiliation  

OBJECTIVE Multiple sclerosis (MS), also called disseminated sclerosis or encephalomyelitis disseminate, is an inflammatory disorder in which the insulating covers of brain nerve cells and the spinal cord are impaired. Emerging evidence has highlighted leukocyte immunoglobulin-like receptor A1 (LILRA1) and its ability to suppress the secretion of various inflammatory factors. METHOD During this study, we explored cell viability, apoptosis, and levels of certain inflammatory factors when silencing LILRA1 in cultured spinal cord cells obtained from mice with MS. A mouse model of experimental autoimmune encephalomyelitis (EAE) was established. A vector system package was used to explore the function of LILRA1 in EAE. The damage of spinal cord tissues was observed by hematoxylin-eosin staining. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay and flow cytometry were applied to detect cell viability, cell cycle distribution, and apoptosis. Enzyme-linked immunosorbent assay and Western blot analysis were adopted to detect the levels of interleukin (IL)-6, IL-17, and tumor necrosis factor-α (TNF-α) in the monocytes. RESULTS Mice with EAE exhibited highly expressed LILRA1, IL-6, IL-17, and TNF-α. LILRA1 silencing was shown to significantly decrease the cell viability and accelerate the cell apoptosis rate in mice with EAE. At the same time, downregulation of LILRA1 significantly decreased the mRNA and protein levels of IL-6, IL-17, and TNF-α in the mouse serum. CONCLUSION The key findings of this study collectively propose that LILRA1 suppression exerts a potent anti-inflammatory effect on MS mice. Overall, LILRA1 downregulation presents a promising therapeutic strategy for the treatment of MS.

中文翻译:

沉默单核细胞中的白细胞免疫球蛋白样受体 A1 可抑制多发性硬化症小鼠的炎症。

目的 多发性硬化症(MS),也称为播散性硬化症或播散性脑脊髓炎,是一种炎症性疾病,其中脑神经细胞和脊髓的绝缘覆盖层受损。新出现的证据强调了白细胞免疫球蛋白样受体 A1 (LILRA1) 及其抑制各种炎症因子分泌的能力。方法 在这项研究中,我们研究了在从 MS 小鼠获得的培养的脊髓细胞中沉默 LILRA1 时的细胞活力、凋亡和某些炎症因子的水平。建立了实验性自身免疫性脑脊髓炎(EAE)小鼠模型。使用载体系统包探索 LILRA1 在 EAE 中的功能。苏木精-伊红染色观察脊髓组织损伤情况。MTT(3-[4,5-二甲基噻唑-2-基]-2,5-二苯基溴化四唑)测定和流式细胞术用于检测细胞活力、细胞周期分布和细胞凋亡。采用酶联免疫吸附法和Western blot分析检测单核细胞中白细胞介素(IL)-6、IL-17和肿瘤坏死因子-α(TNF-α)的水平。结果 EAE 小鼠表现出高表达的 LILRA1、IL-6、IL-17 和 TNF-α。LILRA1 沉默显示显着降低 EAE 小鼠的细胞活力并加速细胞凋亡率。同时,LILRA1 的下调显着降低了小鼠血清中 IL-6、IL-17 和 TNF-α 的 mRNA 和蛋白水平。结论 本研究的主要发现共同表明 LILRA1 抑制对 MS 小鼠具有有效的抗炎作用。全面的,
更新日期:2019-11-01
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