International Immunopharmacology ( IF 5.6 ) Pub Date : 2021-09-28 , DOI: 10.1016/j.intimp.2021.108201 Jessica Gasparello 1 , Elisabetta d'Aversa 1 , Giulia Breveglieri 1 , Monica Borgatti 2 , Alessia Finotti 2 , Roberto Gambari 3
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.
中文翻译:
miR-93-5p agomiR 抑制支气管上皮 IB3-1 细胞中 SARS-CoV-2 刺突蛋白对白细胞介素 8 的体外诱导
COVID-19 的主要临床特征之一是高炎症状态,其特征是细胞因子(如 IL-6 和 TNF-α)、趋化因子(如 IL-8)和生长因子的高表达,并与严重形式的 COVID-19。因此,“细胞因子风暴”的控制是 COVID-19 患者管理中的一个关键问题。在这项研究中,我们报告了证据,表明可以通过模拟 microRNA 的生物活性来抑制 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 IL-8,其表达可以通过使用模拟 miR-93-5p 的分子来修改,miR-93-5p 能够靶向 IL-8 RNA 转录物并调节其活性。