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LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T13","span":{"begin":1862,"end":1879},"obj":"Phenotype"}],"attributes":[{"id":"A13","pred":"hp_id","subj":"T13","obj":"http://www.orpha.net/ORDO/Orphanet_178320"}],"text":"Release of Damage-Associated Molecular Patterns and Proinflammatory Molecules\nThe impaired early IFN response results in high viral propagation that subsequently leads to the induction of a robust proinflammatory response (Davidson et al., 2015). The cytopathic nature of these viruses induces substantial death in infected ATII cells (apoptotic as well as necrotic) which leads to the release of a wide range of damage-associated molecular patterns (DAMPs) and cytotoxic molecules. Similarly, activated AMs also respond to the released DAMPs and act concurrently with PAMPs to amplify the proinflammatory response. A list and role of potential PAMPs, DAMPs, and their respective PRRs have been reviewed previously (Leiva-Juárez et al., 2018).\nCirculating 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).\nIncreased expressions of S100A8, S100A9, and S100A12 calgranulins found in the BALF fluid from COVID-19 patients indicate their potential role in generating the proinflammatory response (Zhou Z. et al., 2020). Further, Zou et al. (2020) showed increased presence of cell-free DNA and citrullinated histones in blood samples obtained from 50 COVID-19 patients. Studies on other inflammatory diseases have shown a close correlation between the presence of these molecules with disease severity (Resman Rus et al., 2016). However, their functional role is yet unexplored, but the increased expression of some of these DAMPs in COVID-19 patients suggests their potential implication in disease pathogenesis. Future studies will clarify the involvement of various other DAMPs in perpetuating the proinflammatory state, and specifically the role of HMGB1.\nIn addition to the secretion of DAMPs, AM and virus infected ATII cells secrete a range of pro-inflammatory molecules (Hussell and Bell, 2014; Glaser et al., 2019). Among these, increased IL-6 levels are consistently detected in cultured cells infected with SARS-CoV and SARS-CoV-2 (Ye et al., 2018; Herold et al., 2020; Liu J. et al., 2020; Liu T. et al., 2020). Notably, levels of TNF-α, IL-8, IL-10, GM-CSF, CXCL10, and CCL5 secreted by infected ATII and activated AMs were also consistently shown to increase during SARS-CoV and SARS-CoV-2 infections (Ward et al., 2005; Huang C. et al., 2020; Patterson et al., 2020). Transcriptional profiling of cytokines and chemokines in normal human lung epithelial cells (NHBE) infected with SARS-CoV-2 revealed increased levels of CCL20, CXCL1, IL-1B, IL-6, CXCL3, CXCL5, CXCL6, CXCL2, CXCL16, and TNF-α by primary lung epithelial cells in response to SARS-CoV-2 infection (Blanco-Melo et al., 2020). Thus, lung resident ATII and AM cells besides being integral to the antiviral response also participate in generating a profound proinflammatory state."}

LitCovid-PubTator

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T249","span":{"begin":0,"end":77},"obj":"Sentence"},{"id":"T250","span":{"begin":78,"end":246},"obj":"Sentence"},{"id":"T251","span":{"begin":247,"end":482},"obj":"Sentence"},{"id":"T252","span":{"begin":483,"end":615},"obj":"Sentence"},{"id":"T253","span":{"begin":616,"end":743},"obj":"Sentence"},{"id":"T254","span":{"begin":744,"end":849},"obj":"Sentence"},{"id":"T255","span":{"begin":850,"end":951},"obj":"Sentence"},{"id":"T256","span":{"begin":952,"end":1152},"obj":"Sentence"},{"id":"T257","span":{"begin":1153,"end":1260},"obj":"Sentence"},{"id":"T258","span":{"begin":1261,"end":1445},"obj":"Sentence"},{"id":"T259","span":{"begin":1446,"end":1611},"obj":"Sentence"},{"id":"T260","span":{"begin":1612,"end":1789},"obj":"Sentence"},{"id":"T261","span":{"begin":1790,"end":1952},"obj":"Sentence"},{"id":"T262","span":{"begin":1953,"end":2245},"obj":"Sentence"},{"id":"T263","span":{"begin":2246,"end":2455},"obj":"Sentence"},{"id":"T264","span":{"begin":2456,"end":2605},"obj":"Sentence"},{"id":"T265","span":{"begin":2606,"end":2764},"obj":"Sentence"},{"id":"T266","span":{"begin":2765,"end":2949},"obj":"Sentence"},{"id":"T267","span":{"begin":2950,"end":3095},"obj":"Sentence"},{"id":"T268","span":{"begin":3096,"end":3260},"obj":"Sentence"},{"id":"T269","span":{"begin":3261,"end":3459},"obj":"Sentence"},{"id":"T270","span":{"begin":3460,"end":3718},"obj":"Sentence"},{"id":"T271","span":{"begin":3719,"end":4041},"obj":"Sentence"},{"id":"T272","span":{"begin":4042,"end":4193},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Release of Damage-Associated Molecular Patterns and Proinflammatory Molecules\nThe impaired early IFN response results in high viral propagation that subsequently leads to the induction of a robust proinflammatory response (Davidson et al., 2015). The cytopathic nature of these viruses induces substantial death in infected ATII cells (apoptotic as well as necrotic) which leads to the release of a wide range of damage-associated molecular patterns (DAMPs) and cytotoxic molecules. Similarly, activated AMs also respond to the released DAMPs and act concurrently with PAMPs to amplify the proinflammatory response. A list and role of potential PAMPs, DAMPs, and their respective PRRs have been reviewed previously (Leiva-Juárez et al., 2018).\nCirculating 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).\nIncreased expressions of S100A8, S100A9, and S100A12 calgranulins found in the BALF fluid from COVID-19 patients indicate their potential role in generating the proinflammatory response (Zhou Z. et al., 2020). Further, Zou et al. (2020) showed increased presence of cell-free DNA and citrullinated histones in blood samples obtained from 50 COVID-19 patients. Studies on other inflammatory diseases have shown a close correlation between the presence of these molecules with disease severity (Resman Rus et al., 2016). However, their functional role is yet unexplored, but the increased expression of some of these DAMPs in COVID-19 patients suggests their potential implication in disease pathogenesis. Future studies will clarify the involvement of various other DAMPs in perpetuating the proinflammatory state, and specifically the role of HMGB1.\nIn addition to the secretion of DAMPs, AM and virus infected ATII cells secrete a range of pro-inflammatory molecules (Hussell and Bell, 2014; Glaser et al., 2019). Among these, increased IL-6 levels are consistently detected in cultured cells infected with SARS-CoV and SARS-CoV-2 (Ye et al., 2018; Herold et al., 2020; Liu J. et al., 2020; Liu T. et al., 2020). Notably, levels of TNF-α, IL-8, IL-10, GM-CSF, CXCL10, and CCL5 secreted by infected ATII and activated AMs were also consistently shown to increase during SARS-CoV and SARS-CoV-2 infections (Ward et al., 2005; Huang C. et al., 2020; Patterson et al., 2020). Transcriptional profiling of cytokines and chemokines in normal human lung epithelial cells (NHBE) infected with SARS-CoV-2 revealed increased levels of CCL20, CXCL1, IL-1B, IL-6, CXCL3, CXCL5, CXCL6, CXCL2, CXCL16, and TNF-α by primary lung epithelial cells in response to SARS-CoV-2 infection (Blanco-Melo et al., 2020). Thus, lung resident ATII and AM cells besides being integral to the antiviral response also participate in generating a profound proinflammatory state."}

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LitCovid-PD-HP

LitCovid-PubTator

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PMC:7736111 / 43400-47593 JSON TXT