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进展型多发性硬化症患者的细胞因子/趋化因子失调是明显的,可以通过钙蛋白酶抑制来调节。

Cytokine/chemokine dysregulation in progressive MS patient is apparent and can be modulated by calpain inhibition.

机构信息

Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.

Department of Neurosurgery, Medical University of South Carolina, 96 Jonathan Lucas St, MSC606, Charleston, SC, 29425, USA.

出版信息

Metab Brain Dis. 2020 Feb;35(2):255-261. doi: 10.1007/s11011-019-00521-1. Epub 2019 Dec 18.

DOI:10.1007/s11011-019-00521-1
PMID:31853829
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9773329/
Abstract

This study examines the cytokine/chemokine profile of a 62-year-old African American male with progressive multiple sclerosis (MS). MRI images of the MS patient demonstrated generalized white matter involvement with multiple lesions in the periventricular area. A 42-plex Discovery Assay® (Eve Technologies) of the patient's plasma and peripheral blood mononuclear cells (PBMCs) supernatant or PBMC-derived T cell supernatant samples from two separate clinic visits revealed vastly differing cytokine/chemokine levels. In addition, certain cytokine/chemokine profiles had notable differences when compared to the larger patient group or patients' PBMCs treated with a calpain inhibitor in vitro. Interestingly, large numbers of cytokines/chemokines and growth factors in MS PBMCs are modulated by calpain inhibition, suggesting the clinical significance of these findings in designing better therapeutics against progressive MS.

摘要

本研究检测了一位 62 岁非裔美国男性进行性多发性硬化症(MS)的细胞因子/趋化因子谱。MS 患者的 MRI 图像显示弥漫性脑白质受累,伴有脑室周围区域的多个病变。使用 Eve Technologies 的 42 plex Discovery Assay®(Eve 技术)对该患者的血浆和外周血单核细胞(PBMC)上清液或来自两次不同就诊的 PBMC 来源 T 细胞上清液样本进行分析,揭示了细胞因子/趋化因子水平的巨大差异。此外,与更大的患者群体或体外用钙蛋白酶抑制剂处理的患者 PBMCs 相比,某些细胞因子/趋化因子谱存在显著差异。有趣的是,钙蛋白酶抑制可调节 MS PBMC 中的大量细胞因子/趋化因子和生长因子,这表明这些发现对于设计针对进行性 MS 的更好治疗方法具有临床意义。

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本文引用的文献

1
Distinct Cytokine and Chemokine Expression in Plasma and Calpeptin-Treated PBMCs of a Relapsing-Remitting Multiple Sclerosis Patient: A Case Report.血浆和钙蛋白酶抑制剂处理的缓解-复发型多发性硬化症患者 PBMC 中的细胞因子和趋化因子的表达谱存在差异:一例报告。
Neurochem Res. 2018 Dec;43(12):2224-2231. doi: 10.1007/s11064-018-2655-z. Epub 2018 Oct 5.
2
Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis.白细胞介素 4 调节小胶质细胞的内稳态并减轻肌萎缩侧索硬化症的早期缓慢进展阶段。
Cell Death Dis. 2018 Feb 14;9(2):250. doi: 10.1038/s41419-018-0288-4.
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Soluble CD40 ligand contributes to blood-brain barrier breakdown and central nervous system inflammation in multiple sclerosis and neuromyelitis optica spectrum disorder.可溶性CD40配体促成多发性硬化症和视神经脊髓炎谱系障碍中的血脑屏障破坏及中枢神经系统炎症。
J Neuroimmunol. 2017 Apr 15;305:102-107. doi: 10.1016/j.jneuroim.2017.01.024. Epub 2017 Feb 4.
4
A regional consensus recommendation on brain atrophy as an outcome measure in multiple sclerosis.关于脑萎缩作为多发性硬化症结局指标的区域共识建议。
BMC Neurol. 2016 Nov 24;16(1):240. doi: 10.1186/s12883-016-0762-5.
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IL4 induces IL6-producing M2 macrophages associated to inhibition of neuroinflammation in vitro and in vivo.白细胞介素4在体内外均可诱导产生白细胞介素6的M2巨噬细胞,从而抑制神经炎症。
J Neuroinflammation. 2016 Jun 7;13(1):139. doi: 10.1186/s12974-016-0596-5.
6
Defining the clinical course of multiple sclerosis: the 2013 revisions.多发性硬化症临床病程的定义:2013年修订版
Neurology. 2014 Jul 15;83(3):278-86. doi: 10.1212/WNL.0000000000000560. Epub 2014 May 28.
7
The Involvement of Calpain in CD4 T Helper Cell Bias in Multple Sclerosis.钙蛋白酶在多发性硬化症中CD4辅助性T细胞偏向性中的作用
J Clin Cell Immunol. 2013 Jun 14;4(4):1000153. doi: 10.4172/2155-9899.1000153.
8
Effects of a novel orally administered calpain inhibitor SNJ-1945 on immunomodulation and neurodegeneration in a murine model of multiple sclerosis.新型口服钙蛋白酶抑制剂 SNJ-1945 对多发性硬化症小鼠模型免疫调节和神经退行性变的影响。
J Neurochem. 2014 Jul;130(2):268-79. doi: 10.1111/jnc.12659. Epub 2014 Feb 12.
9
Synaptic plasticity and PDGF signaling defects underlie clinical progression in multiple sclerosis.突触可塑性和 PDGF 信号缺陷是多发性硬化临床进展的基础。
J Neurosci. 2013 Dec 4;33(49):19112-9. doi: 10.1523/JNEUROSCI.2536-13.2013.
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