HMGB1 as a potential biomarker and therapeutic target for severe COVID-19

COVID-19 has attracted global attention due to its rapid spread around the world with substantial morbidity and associated mortality. Severe COVID-19 can be complicated by the acute respiratory distress syndrome, sepsis and septic shock leading to death. These complications are thought to result fro...

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Bibliographic Details
Published in:Heliyon 2020-12, Vol.6 (12), p.e05672-e05672, Article e05672
Main Authors: Chen, Ruochan, Huang, Yan, Quan, Jun, Liu, Jiao, Wang, Haichao, Billiar, Timothy R., Lotze, Michael T., Zeh, Herbert J., Kang, Rui, Tang, Daolin
Format: Article
Language:English
Subjects:
acute respiratory distress syndrome
biomarkers
blood serum
Cell culture
Cell death
chloroquine
COVID-19
COVID-19 infection
cytokines
death
epithelium
glycyrrhizin
HMGB1
immune system
Immunology
Infectious disease
Inflammation
Microbiology
mortality
nucleoproteins
septic shock
Severe acute respiratory syndrome coronavirus 2
therapeutics
Virology
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Summary:COVID-19 has attracted global attention due to its rapid spread around the world with substantial morbidity and associated mortality. Severe COVID-19 can be complicated by the acute respiratory distress syndrome, sepsis and septic shock leading to death. These complications are thought to result from an overactivation of the immune system, leading to a cytokine storm syndrome associated with multiple organ failure. Here, we report that high mobility group box 1 (HMGB1), a prototypical damage-associated molecular pattern (DAMP) and a central mediator of lethal inflammation, could be a potential target for innovative therapeutic strategies for COVID-19. Serum HMGB1 in severe COVID-19 patients is elevated (189.40 ± 140.88 ng/ml). Exogenous HMGB1 induces the expression of SARS-CoV-2 entry receptor ACE2 in alveolar epithelial cells in an AGER-dependent manner. Importantly, genetic (using AGER siRNA) or pharmacological (using glycyrrhizin, chloroquine, hydroxychloroquine, and FPS-ZM1) inhibition of the HMGB1-AGER pathway blocks ACE2 expression. Thus, HMGB1 inhibitors are likewise promising drug candidates for the treatment of patients suffering from COVID-19. HMGB1; COVID-19; Cell culture; Cell death; Inflammation; Infectious disease; Immunology; Microbiology; Virology
ISSN:2405-8440
2405-8440
DOI:10.1016/j.heliyon.2020.e05672