PMC:7736111 / 44144-45645 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7736111","sourcedb":"PMC","sourceid":"7736111","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7736111","text":"Circulating nuclear and mitochondrial DNA, and histones serve as potential DAMPs during viral infections. These molecules signal via the TLR pathway and induce robust expression of proinflammatory molecules. Among the DAMPs secreted by virus-infected and damaged epithelial cells, the role of high-mobility group box one protein (HMGB1) and S100 are well known (Leiva-Juárez et al., 2018; Gong et al., 2020). HMGB1 after binding to TLR4 induces activation of NF-κB signaling and release of proinflammatory molecules. Additionally, HMGB1 also activates receptors like TREM1/2, and receptors for advanced glycation end products (RAGE) which are also involved in NF-κB activation (Yang and Tracey, 2010). S100 initiates similar downstream signaling after binding with TLR4 and RAGE receptors (Ma et al., 2017), these studies were recently reviewed by Gong et al. (2020). Previous animal studies with other respiratory viruses have shown a close correlation of increased serum HMGB1 levels with lung injury and disease severity (Patel et al., 2018). Similarly, elevated expression of S100A9 was present in patients during acute lung injury mediated by the respiratory syncytial viral (RSV; Foronjy et al., 2016). Although as of now, presence of HMGB1 has no report in COVID-19 patients, the damage in the lung parenchyma in post-mortem biopsies suggests that it is highly likely that this protein may implicate in disease pathogenesis and hyperinflammation (Andersson et al., 2020; Zhang Q. et al., 2020).","tracks":[{"project":"LitCovid-PD-HP","denotations":[{"id":"T13","span":{"begin":1118,"end":1135},"obj":"Phenotype"}],"attributes":[{"id":"A13","pred":"hp_id","subj":"T13","obj":"http://www.orpha.net/ORDO/Orphanet_178320"},{"subj":"T13","pred":"source","obj":"LitCovid-PD-HP"}]},{"project":"LitCovid-PubTator","denotations":[{"id":"1160","span":{"begin":293,"end":316},"obj":"Gene"},{"id":"1161","span":{"begin":330,"end":335},"obj":"Gene"},{"id":"1162","span":{"begin":341,"end":345},"obj":"Gene"},{"id":"1163","span":{"begin":409,"end":414},"obj":"Gene"},{"id":"1164","span":{"begin":432,"end":436},"obj":"Gene"},{"id":"1165","span":{"begin":459,"end":464},"obj":"Gene"},{"id":"1166","span":{"begin":531,"end":536},"obj":"Gene"},{"id":"1167","span":{"begin":567,"end":574},"obj":"Gene"},{"id":"1168","span":{"begin":580,"end":625},"obj":"Gene"},{"id":"1169","span":{"begin":627,"end":631},"obj":"Gene"},{"id":"1170","span":{"begin":660,"end":665},"obj":"Gene"},{"id":"1171","span":{"begin":765,"end":769},"obj":"Gene"},{"id":"1172","span":{"begin":774,"end":778},"obj":"Gene"},{"id":"1173","span":{"begin":973,"end":978},"obj":"Gene"},{"id":"1174","span":{"begin":1080,"end":1086},"obj":"Gene"},{"id":"1175","span":{"begin":1241,"end":1246},"obj":"Gene"},{"id":"1176","span":{"begin":702,"end":706},"obj":"Gene"},{"id":"1177","span":{"begin":1102,"end":1110},"obj":"Species"},{"id":"1178","span":{"begin":1273,"end":1281},"obj":"Species"},{"id":"1179","span":{"begin":903,"end":914},"obj":"Species"},{"id":"1180","span":{"begin":1152,"end":1163},"obj":"Species"},{"id":"1181","span":{"begin":88,"end":104},"obj":"Disease"},{"id":"1182","span":{"begin":236,"end":250},"obj":"Disease"},{"id":"1183","span":{"begin":991,"end":1002},"obj":"Disease"},{"id":"1184","span":{"begin":1124,"end":1135},"obj":"Disease"},{"id":"1185","span":{"begin":1264,"end":1272},"obj":"Disease"}],"attributes":[{"id":"A1160","pred":"tao:has_database_id","subj":"1160","obj":"Gene:6749"},{"id":"A1161","pred":"tao:has_database_id","subj":"1161","obj":"Gene:3146"},{"id":"A1162","pred":"tao:has_database_id","subj":"1162","obj":"Gene:6271"},{"id":"A1163","pred":"tao:has_database_id","subj":"1163","obj":"Gene:3146"},{"id":"A1164","pred":"tao:has_database_id","subj":"1164","obj":"Gene:7099"},{"id":"A1165","pred":"tao:has_database_id","subj":"1165","obj":"Gene:4790"},{"id":"A1166","pred":"tao:has_database_id","subj":"1166","obj":"Gene:3146"},{"id":"A1167","pred":"tao:has_database_id","subj":"1167","obj":"Gene:54210"},{"id":"A1168","pred":"tao:has_database_id","subj":"1168","obj":"Gene:177"},{"id":"A1169","pred":"tao:has_database_id","subj":"1169","obj":"Gene:177"},{"id":"A1170","pred":"tao:has_database_id","subj":"1170","obj":"Gene:4790"},{"id":"A1171","pred":"tao:has_database_id","subj":"1171","obj":"Gene:7099"},{"id":"A1172","pred":"tao:has_database_id","subj":"1172","obj":"Gene:177"},{"id":"A1173","pred":"tao:has_database_id","subj":"1173","obj":"Gene:3146"},{"id":"A1174","pred":"tao:has_database_id","subj":"1174","obj":"Gene:6280"},{"id":"A1175","pred":"tao:has_database_id","subj":"1175","obj":"Gene:3146"},{"id":"A1176","pred":"tao:has_database_id","subj":"1176","obj":"Gene:6271"},{"id":"A1177","pred":"tao:has_database_id","subj":"1177","obj":"Tax:9606"},{"id":"A1178","pred":"tao:has_database_id","subj":"1178","obj":"Tax:9606"},{"id":"A1179","pred":"tao:has_database_id","subj":"1179","obj":"Tax:12814"},{"id":"A1180","pred":"tao:has_database_id","subj":"1180","obj":"Tax:12814"},{"id":"A1181","pred":"tao:has_database_id","subj":"1181","obj":"MESH:D001102"},{"id":"A1182","pred":"tao:has_database_id","subj":"1182","obj":"MESH:D001102"},{"id":"A1183","pred":"tao:has_database_id","subj":"1183","obj":"MESH:D055370"},{"id":"A1184","pred":"tao:has_database_id","subj":"1184","obj":"MESH:D055370"},{"id":"A1185","pred":"tao:has_database_id","subj":"1185","obj":"MESH:C000657245"},{"subj":"1160","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1161","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1162","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1163","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1164","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1165","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1166","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1167","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1168","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1169","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1170","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1171","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1172","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1173","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1174","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1175","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1176","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1177","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1178","pred":"source","obj":"LitCovid-PubTator"},{"subj":"11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