微泡
炎症
小RNA
肿瘤坏死因子α
2019年冠状病毒病(COVID-19)
冠状病毒
癌症研究
生物
肺
免疫学
医学
病理
生物化学
疾病
内科学
基因
传染病(医学专业)
作者
Yuee Teng,Fangyi Xu,Xiangcheng Zhang,Jingbo Mu,Mohammed Sayed,Xin Hu,Chao Lei,Mukesh K. Sriwastva,Anil Kumar,Kumaran Sundaram,Lifeng Zhang,Juw Won Park,Shao Yu Chen,Shuangqin Zhang,Jun Yan,Michael L. Merchant,Xiang Zhang,Craig J. McClain,Jennifer K. Wolfe,Robert S. Adcock,Donghoon Chung,Kenneth E. Palmer,Huang Ge Zhang
标识
DOI:10.1016/j.ymthe.2021.05.005
摘要
Lung inflammation is a hallmark of coronavirus disease 2019 (COVID-19). In this study, we show that mice develop inflamed lung tissue after being administered exosomes released from the lung epithelial cells exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp12 and Nsp13 (exosomesNsp12Nsp13). Mechanistically, we show that exosomesNsp12Nsp13 are taken up by lung macrophages, leading to activation of nuclear factor κB (NF-κB) and the subsequent induction of an array of inflammatory cytokines. Induction of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β from exosomesNsp12Nsp13-activated lung macrophages contributes to inducing apoptosis in lung epithelial cells. Induction of exosomesNsp12Nsp13-mediated lung inflammation was abolished with ginger exosome-like nanoparticle (GELN) microRNA (miRNA aly-miR396a-5p. The role of GELNs in inhibition of the SARS-CoV-2-induced cytopathic effect (CPE) was further demonstrated via GELN aly-miR396a-5p- and rlcv-miR-rL1-28-3p-mediated inhibition of expression of Nsp12 and spike genes, respectively. Taken together, our results reveal exosomesNsp12Nsp13 as potentially important contributors to the development of lung inflammation, and GELNs are a potential therapeutic agent to treat COVID-19.
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