Plant-derived exosomal microRNAs inhibit lung inflammation induced by exosomes SARS-CoV-2 Nsp12.

Autor:	Teng Y; James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA. Electronic address: yun.teng@louisville.edu., Xu F; James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA., Zhang X; James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA; Department of ICU, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu 223300, China., Mu J; James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA., Sayed M; Department of Computer Engineering and Computer Science, University of Louisville, Louisville, KY 40202, USA., Hu X; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Lei C; James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA., Sriwastva M; James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA., Kumar A; James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA., Sundaram K; James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA., Zhang L; James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA., Park JW; Department of Computer Engineering and Computer Science, University of Louisville, Louisville, KY 40202, USA; KBRIN Bioinformatics Core, University of Louisville, Louisville, KY 40202, USA., Chen SY; Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40202, USA., Zhang S; Peeples Cancer Institute at Hamilton Medical Center, Dalton, GA 30720, USA., Yan J; James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA., Merchant ML; Kidney Disease Program and Clinical Proteomics Center, University of Louisville, Louisville, KY 40202, USA., Zhang X; Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40202, USA., McClain CJ; Robley Rex Veterans Affairs Medical Center, Louisville, KY 40206, USA; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Louisville, Louisville, KY 40202, USA., Wolfe JK; Center for Predictive Medicine for Emerging Infectious Diseases, School of Medicine, University of Louisville, Louisville, KY 40202, USA., Adcock RS; Center for Predictive Medicine for Emerging Infectious Diseases, School of Medicine, University of Louisville, Louisville, KY 40202, USA., Chung D; Department of Microbiology & Immunology, University of Louisville, Louisville, KY 40202, USA; Center for Predictive Medicine for Emerging Infectious Diseases, School of Medicine, University of Louisville, Louisville, KY 40202, USA., Palmer KE; Center for Predictive Medicine for Emerging Infectious Diseases, School of Medicine, University of Louisville, Louisville, KY 40202, USA; Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40202, USA., Zhang HG; Robley Rex Veterans Affairs Medical Center, Louisville, KY 40206, USA; Department of Microbiology & Immunology, University of Louisville, Louisville, KY 40202, USA; James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA. Electronic address: h0zhan17@louisville.edu.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2021 Aug 04; Vol. 29 (8), pp. 2424-2440. Date of Electronic Publication: 2021 May 11.
DOI:	10.1016/j.ymthe.2021.05.005
Abstrakt:	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 (exosomes Nsp12Nsp13 ). Mechanistically, we show that exosomes Nsp12Nsp13 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 exosomes Nsp12Nsp13 -activated lung macrophages contributes to inducing apoptosis in lung epithelial cells. Induction of exosomes Nsp12Nsp13 -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 exosomes Nsp12Nsp13 as potentially important contributors to the development of lung inflammation, and GELNs are a potential therapeutic agent to treat COVID-19. Competing Interests: Declaration of interests The authors declare no competing interests. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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