SARS-CoV-2 infection can cause cytokine storm and may overshoot immunity in humans; however, it remains to be determined whether virus-induced soluble mediators from infected cells are carried by exosomes as vehicles to distant organs and cause tissue damage in COVID-19 patients. We took an unbiased proteomic approach for analyses of exosomes isolated from plasma of healthy volunteers and COVID-19 patients. Our results revealed that tenascin-C (TNC) and fibrinogen-β (FGB) are highly abundant in exosomes from COVID-19 patients’ plasma compared with that of healthy normal controls. Since TNC and FGB stimulate pro-inflammatory cytokines via the Nuclear factor-κB (NF-κB) pathway, we examined the status of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C–C motif chemokine ligand 5 (CCL5) expression upon exposure of hepatocytes to exosomes from COVID-19 patients and observed significant increase compared with that from healthy subjects. Together, our results demonstrate that TNC and FGB are transported through plasma exosomes and potentially trigger pro-inflammatory cytokine signaling in cells of distant organ.
【저자키워드】 COVID-19, mass spectrometry, Cytokines, Pathogenesis, Exosomes, tenascin-C, fibrinogen-β, 【초록키워드】 Exosome, Cytokine storm, Immunity, IL-6, SARS-COV-2 infection, interleukin-6, chemokine, pathway, plasma, expression, proteomic, COVID-19 patients, TNF-α, NF-κB, Signaling, Ligand, Analysis, COVID-19 patient, tumor necrosis factor-α, tissue damage, significant increase, healthy subjects, CCL5, pro-inflammatory cytokine, infected cell, organ, motif, hepatocyte, approach, controls, Cell, examined, carried, healthy, stimulate, transported, FGB, healthy volunteer, overshoot, TNC, 【제목키워드】 Exosome, signal, Distant,