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KMID : 0923620230230030026
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Immune Network
2023 Volume.23 No. 3 p.26 ~ p.26
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SARS-CoV-2 Infection Induces HMGB1 Secretion Through Post-Translational Modification and PANoptosis
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Kwak Man-Sup
Choi Seo-Yeon
Kim Ji-Seon
Lee Hoo-Jung
Park In-Ho
Oh Joo-Yeon
Duong Ngoc Mai
Cho Nam-Hyuk
Nam Ki-Taek
Shin Jeon-Soo
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Abstract
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces excessive pro-inflammatory cytokine release and cell death, leading to organ damage and mortality. High-mobility group box 1 (HMGB1) is one of the damage-associated molecular patterns that can be secreted by pro-inflammatory stimuli, including viral infections, and its excessive secretion levels are related to a variety of inflammatory diseases. Here, the aim of the study was to show that SARS-CoV-2 infection induced HMGB1 secretion via active and passive release. Active HMGB1 secretion was mediated by post-translational modifications, such as acetylation, phosphorylation, and oxidation in HEK293E/ACE2-C-GFP and Calu-3 cells during SARS-CoV-2 infection. Passive release of HMGB1 has been linked to various types of cell death; however, we demonstrated for the first time that PANoptosis, which integrates other cell death pathways, including pyroptosis, apoptosis, and necroptosis, is related to passive HMGB1 release during SARS-CoV-2 infection. In addition, cytoplasmic translocation and extracellular secretion or release of HMGB1 were confirmed via immunohistochemistry and immunofluorescence in the lung tissues of humans and angiotensin-converting enzyme 2-overexpressing mice infected with SARS-CoV-2.
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KEYWORD
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HMGB1 protein, Severe acute respiratory syndrome coronavirus 2, Post-translational modification, PANoptosis
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