Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces inflammatory response, cytokine storm, venous thromboembolism, coagulopathy, and multiple organ damage. Resting endothelial cells prevent coagulation, control blood flow, and inhibit inflammation. However, it remains unknown how SARS-CoV-2 induces strong molecular signals in distant cells for immunopathogenesis. In this study, we examined the consequence of human endothelial cells, microvascular endothelial cells (HMEC-1), and liver endothelial cells (TMNK-1) to exosomes isolated from plasma of mild or severe COVID-19 patients. We observed a significant induction of NLRP3, caspase-1, and interleukin-1β (IL-1β) mRNA expression in endothelial cells following exposure to exosomes from severe COVID-19 patients compared with that from patients with mild disease or healthy donors. Activation of caspase-1 was noted in the endothelial cell culture medium following exposure to the COVID-19 exosomes. Furthermore, COVID-19 exosomes significantly induced mature IL-1β secretion in both HMEC-1 and TMNK-1 endothelial cell culture medium. Thus, our results demonstrated for the first time that exosomes from COVID-19 plasma trigger NLRP3 inflammasome in endothelial cells of distant organs resulting in IL-1β secretion and inflammatory response. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global health problem. Although the vaccine controls infection, understanding the molecular mechanism of pathogenesis will help in developing future therapies. Furthermore, several investigators predicted the involvement of endothelial cell-related inflammation in SARS-CoV-2 infection and using extracellular vesicles as a cargo to carry a drug or vaccine for combating SARS-CoV-2 infection. However, the mechanism by which endothelial cells are inflamed remains unknown. Our present study highlights that exosomes from severe COVID-19 patients can enhance inflammasome activity in distant endothelial cells for augmentation of immunopathogenesis and opens an avenue for developing therapies.
Keywords: COVID-19; NLRP3; SARS-CoV-2; endothelial cells; exosomes; inflammasome.
【저자키워드】 COVID-19, SARS-CoV-2, Exosomes, endothelial cells, NLRP3, inflammasome., 【초록키워드】 severe acute respiratory syndrome coronavirus 2, Inflammation, Exosome, Vaccine, Cytokine storm, coronavirus, Pathogenesis, SARS-COV-2 infection, Infection, Extracellular vesicles, Exosomes, drug, molecular mechanism, severe acute respiratory syndrome Coronavirus, coronavirus 2, Venous Thromboembolism, NLRP3 inflammasome, Coagulation, Coagulopathy, Severe acute respiratory syndrome, Health, interleukin, Culture, endothelial cells, Immunopathogenesis, Patient, Control, Mild, plasma, Inflammasome, caspase-1, extracellular vesicle, culture medium, molecular, respiratory, liver, mechanism, caspase, Therapies, Mild disease, interleukin-1β, NLRP3, Endothelial cell, IL-1β, Inflammatory response, Multiple organ damage, Trigger, blood flow, health problem, exposure to, opens, endothelial, acute respiratory syndrome, acute respiratory syndrome coronavirus, healthy donors, medium, secretion, severe COVID-19 patients, help, investigator, organ damage, augmentation, organ, mRNA expression, cargo, Prevent, Cell, highlight, Activation of caspase-1, combating, ENhance, resting, resulting, predicted, examined, significantly, inhibit, demonstrated, induce, the vaccine, severe COVID-19 patient, with mild disease, 【제목키워드】 Exosome, Circulatory,