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Plasma microparticles from patients with systemic lupus erythematosus modulate the content of miRNAs in U937 cells
Immunology ( IF 6.4 ) Pub Date : 2021-05-18 , DOI: 10.1111/imm.13366
Liseth Carmona-Pérez 1 , Mauricio Rojas 1, 2 , Carlos Muñoz-Vahos 3, 4 , Adiana Vanegas-García 3, 4 , Gloria Vásquez 1, 4
Affiliation  

In systemic lupus erythematosus (SLE), the clearance of apoptotic cells and microparticles (MPs) is reduced. Some MPs contain molecules that can modulate immune responses. This study aimed to evaluate the presence of miR-126 and miR-146a in plasma MPs of patients with SLE (SLE MPs) and analyse the ability of MPs to modulate some events in the promonocytic U937 cell line. Circulating MPs were isolated from plasma samples of healthy controls (HCs), patients with SLE and other autoimmune diseases (OAD). MPs were analysed for size and cell origin by flow cytometry and content of miR-126 and miR-146a by RT-qPCR. MPs were then added to U937 cell cultures to evaluate changes in cell phenotype, cytokine expression, content of miR-126 and miR-146a, and levels of IRF5. Patients with active SLE (aSLE) showed an increase in concentration of plasma MPs that positively correlated with the SLEDAI (SLE Disease Activity Index) score. CD14+ MPs were significantly more abundant in patients with SLE than HCs. SLE MPs contained decreased levels of miR-146a, but the miR-126 content in aSLE MPs was increased. The miR-126 content in SLE MPs correlated positively with the SLEDAI score. The treatment of U937 cells with MPs from HCs and patients induced reduced expression of HLA-DR, CD18 and CD119, increased frequency of IL-6+ and TNF-α+ cells, accumulation of IL-8 in culture supernatants, increased miR-126 levels and decreased miR-146a content, but no change in the expression of IRF5. These findings suggest that plasma MPs, especially SLE MPs, could modulate some biological events in U937 cells.

中文翻译:

系统性红斑狼疮患者血浆微粒调节 U937 细胞中 miRNA 的含量

在系统性红斑狼疮 (SLE) 中,凋亡细胞和微粒 (MP) 的清除率降低。一些 MP 含有可以调节免疫反应的分子。本研究旨在评估 SLE 患者血浆 MP(SLE MP)中 miR-126 和 miR-146a 的存在,并分析 MP 调节早单核 U937 细胞系中某些事件的能力。从健康对照 (HC)、系统性红斑狼疮 (SLE) 和其他自身免疫性疾病 (OAD) 患者的血浆样本中分离出循环 MP。通过流式细胞术分析 MP 的大小和细胞来源,并通过 RT-qPCR 分析 miR-126 和 miR-146a 的含量。然后将 MP 添加到 U937 细胞培养物中,以评估细胞表型、细胞因子表达、miR-126 和 miR-146a 含量以及 IRF5 水平的变化。活动性 SLE (aSLE) 患者血浆 MP 浓度升高,与 SLEDAI(SLE 疾病活动指数)评分呈正相关。SLE 患者中 CD14+ MP 的含量显着高于 HC 患者。SLE MP 中 miR-146a 的含量降低,但 aSLE MP 中 miR-126 的含量增加。SLE MPs 中的 miR-126 含量与 SLEDAI 评分呈正相关。用来自 HC 和患者的 MP 处理 U937 细胞,诱导 HLA-DR、CD18 和 CD119 表达降低,IL-6+ 和 TNF-α+ 细胞频率增加,培养物上清液中 IL-8 积累,miR-126 增加水平和 miR-146a 含量降低,但 IRF5 的表达没有变化。这些发现表明血浆 MP,尤其是 SLE MP,可以调节 U937 细胞中的一些生物事件。
更新日期:2021-05-18
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