Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy; Research Center for Innovative Therapies of Cystic Fibrosis, University of Ferrara, Italy.
Int Immunopharmacol. 2021 Dec;101(Pt B):108201. doi: 10.1016/j.intimp.2021.108201. Epub 2021 Sep 28.
One of the major clinical features of COVID-19 is a hyperinflammatory state, which is characterized by high expression of cytokines (such as IL-6 and TNF-α), chemokines (such as IL-8) and growth factors and is associated with severe forms of COVID-19. For this reason, the control of the "cytokine storm" represents a key issue in the management of COVID-19 patients. In this study we report evidence that the release of key proteins of the COVID-19 "cytokine storm" can be inhibited by mimicking the biological activity of microRNAs. The major focus of this report is on IL-8, whose expression can be modified by the employment of a molecule mimicking miR-93-5p, which is able to target the IL-8 RNA transcript and modulate its activity. The results obtained demonstrate that the production of IL-8 protein is enhanced in bronchial epithelial IB3-1 cells by treatment with the SARS-CoV-2 Spike protein and that IL-8 synthesis and extracellular release can be strongly reduced using an agomiR molecule mimicking miR-93-5p.
新型冠状病毒病（COVID-19）的主要临床特征之一是过度炎症状态，其特征是细胞因子（如白细胞介素-6 和肿瘤坏死因子-α）、趋化因子（如白细胞介素-8）和生长因子表达增加，与 COVID-19 的严重形式有关。因此，控制“细胞因子风暴”是 COVID-19 患者治疗的关键问题。在这项研究中，我们报告了证据表明，通过模拟 microRNAs 的生物学活性，可以抑制 COVID-19“细胞因子风暴”的关键蛋白的释放。本报告的主要重点是白细胞介素-8（IL-8），其表达可以通过使用模拟 miR-93-5p 的分子来修饰，该分子能够靶向 IL-8 RNA 转录本并调节其活性。获得的结果表明，用 SARS-CoV-2 刺突蛋白处理可增强支气管上皮 IB3-1 细胞中白细胞介素-8 蛋白的产生，并且使用模拟 miR-93-5p 的 agomiR 分子可强烈减少白细胞介素-8 的合成和细胞外释放。
