CCL2 Promotes Novel Coronavirus-Mediated Inflammatory Responses in Macrophages.

IF 1.2 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL
Fang Ding, Muwei Dai, Xichun Kang, Xin Zhang, Li Li, Lei Zhao, Ping Jiang, Huixia Gao, Huimin Yan
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Abstract

Purpose: The hyperinflammatory response is one of the main complications associated with novel coronavirus disease 2019 (COVID-19), and there is no effective treatment for cytokine storm. Therefore, it is important to investigate the key genes associated with severity of the disease.

Methods: In this study, we used a microarray data set to analyze the key genes associated with severe illness in patients with COVID-19. The proportion of immune cells was determined using the CIBERSORT algorithm. The key genes were further verified by detecting the levels of cytokines and chemokines in the serum of patients. Additionally, macrophages were stimulated with SARS-CoV-2 spike protein and chemokine ligand (CCL) 2. The expression of cytokines, ERK1/2, and NF-κB in macrophages was detected.

Results: Four hub genes were identified. Among them, C-C motif chemokine receptor 2 (CCR2) was an upregulated hub gene, while killer cell lectin-like receptor subfamily K member 1 (KLRK1), macrophage colony-stimulating factor receptor (CSF1R), and CD3D human recombinant protein (CD3D) were downregulated genes. Immune cell type identification found that the proportion of monocytes was higher in patients with severe COVID-19 than that in controls. Moreover, levels of CCL2 were significantly higher in patients with COVID-19. When stimulated with SARS-CoV-2 S protein and CCL2, macrophages secreted more inflammatory cytokines. The expression level of ERK1/2 was elevated.

Conclusions: These results suggested that S protein and CCL2 may mediate macrophage inflammatory responses through the ERK1/2 signaling pathway. This study provides a basis for clinical treatment and improves the prognosis of critically ill patients with COVID-19.

CCL2在巨噬细胞中促进新型冠状病毒介导的炎症反应。
目的:高炎症反应是2019年新型冠状病毒病(新冠肺炎)的主要并发症之一,细胞因子风暴尚无有效治疗方法。因此,研究与疾病严重程度相关的关键基因是很重要的。方法:在本研究中,我们使用微阵列数据集来分析与新冠肺炎患者重症相关的关键基因。免疫细胞的比例使用CIBERSORT算法来确定。通过检测患者血清中细胞因子和趋化因子的水平,进一步验证了关键基因。此外,巨噬细胞受到严重急性呼吸系统综合征冠状病毒2型刺突蛋白和趋化因子配体(CCL)2的刺激。检测巨噬细胞中细胞因子、ERK1/2和NF-κB的表达。结果:共鉴定出4个hub基因。其中,C-C基序趋化因子受体2(CCR2)是上调的枢纽基因,而杀伤细胞凝集素样受体亚家族K成员1(KLRK1)、巨噬细胞集落刺激因子受体(CSF1R)和CD3D人重组蛋白(CD3D)是下调的基因。免疫细胞类型鉴定发现,重症新冠肺炎患者的单核细胞比例高于对照组。此外,新冠肺炎患者的CCL2水平显著升高。当受到严重急性呼吸系统综合征冠状病毒2型S蛋白和CCL2的刺激时,巨噬细胞分泌更多的炎性细胞因子。ERK1/2的表达水平升高。结论:S蛋白和CCL2可能通过ERK1/2信号通路介导巨噬细胞炎症反应。该研究为新冠肺炎危重患者的临床治疗和改善预后提供了依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical and Investigative Medicine
Clinical and Investigative Medicine 医学-医学:研究与实验
CiteScore
1.50
自引率
12.50%
发文量
18
审稿时长
>12 weeks
期刊介绍: Clinical and Investigative Medicine (CIM), publishes original work in the field of Clinical Investigation. Original work includes clinical or laboratory investigations and clinical reports. Reviews include information for Continuing Medical Education (CME), narrative review articles, systematic reviews, and meta-analyses.
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