PMC:7565665 / 45809-47945 JSON TXT

Annnotations TAB JSON ListView MergeView

LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T81","span":{"begin":692,"end":696},"obj":"Body_part"},{"id":"T82","span":{"begin":1320,"end":1324},"obj":"Body_part"},{"id":"T83","span":{"begin":1325,"end":1331},"obj":"Body_part"}],"attributes":[{"id":"A81","pred":"uberon_id","subj":"T81","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A82","pred":"uberon_id","subj":"T82","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A83","pred":"uberon_id","subj":"T83","obj":"http://purl.obolibrary.org/obo/UBERON_0000479"}],"text":"The lack of functional CFTR in macrophages results in an increased production of inflammatory cytokines, and impaired pathogen clearance capacity. The diminished expression of HLA-DQ and HLA-DR (MHC-II molecules) on monocytes derived from ΔF508-CFTR homozygous CF subjects [166], might explain the impaired pathogen clearance ability of CF macrophages. In addition, CFTR deficiency has been implicated in diminished Treg effector function and a more pronounced Th2-biased immune response [167]. The CF defect has also been shown to affect the activation of neutrophils [168], which are the cells responsible for the first line of defense in the airways. Although, airway epithelial cells and lung-resident macrophages sense the invading pathogens and secrete a plethora of factors to induce the recruitment and activation of neutrophils, neutrophils from CF subjects have diminished phagocytic potentials by virtue of the reduced cell surface expression of toll-like receptors (TLRs) and disrupted chloride transport to the phagolysosome [169,170]. Thus the CFTR mutation in CF results in impaired bacterial killing [171]. Moreover, CF neutrophils also demonstrate an increased capacity to release their primary granule contents such as MPO and neutrophil elastase (NE). The uncontrolled release of these enzymes causes lung tissue damage and severe airway inflammation. We have shown that P. aeruginosa LPS-induced MPO levels can be reduced by treatment with the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), plausibly by restoring the trafficking of ΔF508-CFTR, suggesting that a functional CFTR is required to keep a tab on uncontrolled neutrophil activation [172]. Mechanistically, an absence or dysfunction of CFTR in neutrophils results in the deactivation of the guanosine triphosphate (GTP)-binding protein Rab27a, which causes impaired granule exocytosis [168,172]. Several studies now agree that the pharmacological inhibition of CFTR or the mutant ΔF508-CFTR is sufficient to cause deregulated neutrophil activation via the activation of the NFκB pathway, resulting in hyperinflammation [172]."}

LitCovid-PD-MONDO

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T358","span":{"begin":261,"end":263},"obj":"Disease"},{"id":"T359","span":{"begin":337,"end":339},"obj":"Disease"},{"id":"T360","span":{"begin":499,"end":501},"obj":"Disease"},{"id":"T361","span":{"begin":855,"end":857},"obj":"Disease"},{"id":"T362","span":{"begin":1075,"end":1077},"obj":"Disease"},{"id":"T363","span":{"begin":1133,"end":1135},"obj":"Disease"},{"id":"T364","span":{"begin":1357,"end":1369},"obj":"Disease"}],"attributes":[{"id":"A358","pred":"mondo_id","subj":"T358","obj":"http://purl.obolibrary.org/obo/MONDO_0009061"},{"id":"A359","pred":"mondo_id","subj":"T359","obj":"http://purl.obolibrary.org/obo/MONDO_0009061"},{"id":"A360","pred":"mondo_id","subj":"T360","obj":"http://purl.obolibrary.org/obo/MONDO_0009061"},{"id":"A361","pred":"mondo_id","subj":"T361","obj":"http://purl.obolibrary.org/obo/MONDO_0009061"},{"id":"A362","pred":"mondo_id","subj":"T362","obj":"http://purl.obolibrary.org/obo/MONDO_0009061"},{"id":"A363","pred":"mondo_id","subj":"T363","obj":"http://purl.obolibrary.org/obo/MONDO_0009061"},{"id":"A364","pred":"mondo_id","subj":"T364","obj":"http://purl.obolibrary.org/obo/MONDO_0021166"}],"text":"The lack of functional CFTR in macrophages results in an increased production of inflammatory cytokines, and impaired pathogen clearance capacity. The diminished expression of HLA-DQ and HLA-DR (MHC-II molecules) on monocytes derived from ΔF508-CFTR homozygous CF subjects [166], might explain the impaired pathogen clearance ability of CF macrophages. In addition, CFTR deficiency has been implicated in diminished Treg effector function and a more pronounced Th2-biased immune response [167]. The CF defect has also been shown to affect the activation of neutrophils [168], which are the cells responsible for the first line of defense in the airways. Although, airway epithelial cells and lung-resident macrophages sense the invading pathogens and secrete a plethora of factors to induce the recruitment and activation of neutrophils, neutrophils from CF subjects have diminished phagocytic potentials by virtue of the reduced cell surface expression of toll-like receptors (TLRs) and disrupted chloride transport to the phagolysosome [169,170]. Thus the CFTR mutation in CF results in impaired bacterial killing [171]. Moreover, CF neutrophils also demonstrate an increased capacity to release their primary granule contents such as MPO and neutrophil elastase (NE). The uncontrolled release of these enzymes causes lung tissue damage and severe airway inflammation. We have shown that P. aeruginosa LPS-induced MPO levels can be reduced by treatment with the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), plausibly by restoring the trafficking of ΔF508-CFTR, suggesting that a functional CFTR is required to keep a tab on uncontrolled neutrophil activation [172]. Mechanistically, an absence or dysfunction of CFTR in neutrophils results in the deactivation of the guanosine triphosphate (GTP)-binding protein Rab27a, which causes impaired granule exocytosis [168,172]. Several studies now agree that the pharmacological inhibition of CFTR or the mutant ΔF508-CFTR is sufficient to cause deregulated neutrophil activation via the activation of the NFκB pathway, resulting in hyperinflammation [172]."}

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PubTator

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T150","span":{"begin":761,"end":769},"obj":"Phenotype"}],"attributes":[{"id":"A150","pred":"hp_id","subj":"T150","obj":"http://purl.obolibrary.org/obo/HP_0001050"}],"text":"The lack of functional CFTR in macrophages results in an increased production of inflammatory cytokines, and impaired pathogen clearance capacity. The diminished expression of HLA-DQ and HLA-DR (MHC-II molecules) on monocytes derived from ΔF508-CFTR homozygous CF subjects [166], might explain the impaired pathogen clearance ability of CF macrophages. In addition, CFTR deficiency has been implicated in diminished Treg effector function and a more pronounced Th2-biased immune response [167]. The CF defect has also been shown to affect the activation of neutrophils [168], which are the cells responsible for the first line of defense in the airways. Although, airway epithelial cells and lung-resident macrophages sense the invading pathogens and secrete a plethora of factors to induce the recruitment and activation of neutrophils, neutrophils from CF subjects have diminished phagocytic potentials by virtue of the reduced cell surface expression of toll-like receptors (TLRs) and disrupted chloride transport to the phagolysosome [169,170]. Thus the CFTR mutation in CF results in impaired bacterial killing [171]. Moreover, CF neutrophils also demonstrate an increased capacity to release their primary granule contents such as MPO and neutrophil elastase (NE). The uncontrolled release of these enzymes causes lung tissue damage and severe airway inflammation. We have shown that P. aeruginosa LPS-induced MPO levels can be reduced by treatment with the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), plausibly by restoring the trafficking of ΔF508-CFTR, suggesting that a functional CFTR is required to keep a tab on uncontrolled neutrophil activation [172]. Mechanistically, an absence or dysfunction of CFTR in neutrophils results in the deactivation of the guanosine triphosphate (GTP)-binding protein Rab27a, which causes impaired granule exocytosis [168,172]. Several studies now agree that the pharmacological inhibition of CFTR or the mutant ΔF508-CFTR is sufficient to cause deregulated neutrophil activation via the activation of the NFκB pathway, resulting in hyperinflammation [172]."}

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T622","span":{"begin":23,"end":27},"obj":"http://purl.obolibrary.org/obo/GO_0005260"},{"id":"T623","span":{"begin":245,"end":249},"obj":"http://purl.obolibrary.org/obo/GO_0005260"},{"id":"T624","span":{"begin":366,"end":370},"obj":"http://purl.obolibrary.org/obo/GO_0005260"},{"id":"T625","span":{"begin":472,"end":487},"obj":"http://purl.obolibrary.org/obo/GO_0006955"},{"id":"T626","span":{"begin":998,"end":1016},"obj":"http://purl.obolibrary.org/obo/GO_0006821"},{"id":"T627","span":{"begin":1007,"end":1016},"obj":"http://purl.obolibrary.org/obo/GO_0006810"},{"id":"T628","span":{"begin":1058,"end":1062},"obj":"http://purl.obolibrary.org/obo/GO_0005260"},{"id":"T629","span":{"begin":1357,"end":1369},"obj":"http://purl.obolibrary.org/obo/GO_0006954"},{"id":"T630","span":{"begin":1590,"end":1594},"obj":"http://purl.obolibrary.org/obo/GO_0005260"},{"id":"T631","span":{"begin":1625,"end":1629},"obj":"http://purl.obolibrary.org/obo/GO_0005260"},{"id":"T632","span":{"begin":1672,"end":1693},"obj":"http://purl.obolibrary.org/obo/GO_0042119"},{"id":"T633","span":{"begin":1747,"end":1751},"obj":"http://purl.obolibrary.org/obo/GO_0005260"},{"id":"T634","span":{"begin":1885,"end":1895},"obj":"http://purl.obolibrary.org/obo/GO_0006887"},{"id":"T635","span":{"begin":1972,"end":1976},"obj":"http://purl.obolibrary.org/obo/GO_0005260"},{"id":"T636","span":{"begin":1997,"end":2001},"obj":"http://purl.obolibrary.org/obo/GO_0005260"},{"id":"T637","span":{"begin":2037,"end":2058},"obj":"http://purl.obolibrary.org/obo/GO_0042119"}],"text":"The lack of functional CFTR in macrophages results in an increased production of inflammatory cytokines, and impaired pathogen clearance capacity. The diminished expression of HLA-DQ and HLA-DR (MHC-II molecules) on monocytes derived from ΔF508-CFTR homozygous CF subjects [166], might explain the impaired pathogen clearance ability of CF macrophages. In addition, CFTR deficiency has been implicated in diminished Treg effector function and a more pronounced Th2-biased immune response [167]. The CF defect has also been shown to affect the activation of neutrophils [168], which are the cells responsible for the first line of defense in the airways. Although, airway epithelial cells and lung-resident macrophages sense the invading pathogens and secrete a plethora of factors to induce the recruitment and activation of neutrophils, neutrophils from CF subjects have diminished phagocytic potentials by virtue of the reduced cell surface expression of toll-like receptors (TLRs) and disrupted chloride transport to the phagolysosome [169,170]. Thus the CFTR mutation in CF results in impaired bacterial killing [171]. Moreover, CF neutrophils also demonstrate an increased capacity to release their primary granule contents such as MPO and neutrophil elastase (NE). The uncontrolled release of these enzymes causes lung tissue damage and severe airway inflammation. We have shown that P. aeruginosa LPS-induced MPO levels can be reduced by treatment with the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), plausibly by restoring the trafficking of ΔF508-CFTR, suggesting that a functional CFTR is required to keep a tab on uncontrolled neutrophil activation [172]. Mechanistically, an absence or dysfunction of CFTR in neutrophils results in the deactivation of the guanosine triphosphate (GTP)-binding protein Rab27a, which causes impaired granule exocytosis [168,172]. Several studies now agree that the pharmacological inhibition of CFTR or the mutant ΔF508-CFTR is sufficient to cause deregulated neutrophil activation via the activation of the NFκB pathway, resulting in hyperinflammation [172]."}

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T241","span":{"begin":0,"end":146},"obj":"Sentence"},{"id":"T242","span":{"begin":147,"end":352},"obj":"Sentence"},{"id":"T243","span":{"begin":353,"end":494},"obj":"Sentence"},{"id":"T244","span":{"begin":495,"end":653},"obj":"Sentence"},{"id":"T245","span":{"begin":654,"end":1048},"obj":"Sentence"},{"id":"T246","span":{"begin":1049,"end":1122},"obj":"Sentence"},{"id":"T247","span":{"begin":1123,"end":1270},"obj":"Sentence"},{"id":"T248","span":{"begin":1271,"end":1370},"obj":"Sentence"},{"id":"T249","span":{"begin":1371,"end":1700},"obj":"Sentence"},{"id":"T250","span":{"begin":1701,"end":1906},"obj":"Sentence"},{"id":"T251","span":{"begin":1907,"end":2136},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"The lack of functional CFTR in macrophages results in an increased production of inflammatory cytokines, and impaired pathogen clearance capacity. The diminished expression of HLA-DQ and HLA-DR (MHC-II molecules) on monocytes derived from ΔF508-CFTR homozygous CF subjects [166], might explain the impaired pathogen clearance ability of CF macrophages. In addition, CFTR deficiency has been implicated in diminished Treg effector function and a more pronounced Th2-biased immune response [167]. The CF defect has also been shown to affect the activation of neutrophils [168], which are the cells responsible for the first line of defense in the airways. Although, airway epithelial cells and lung-resident macrophages sense the invading pathogens and secrete a plethora of factors to induce the recruitment and activation of neutrophils, neutrophils from CF subjects have diminished phagocytic potentials by virtue of the reduced cell surface expression of toll-like receptors (TLRs) and disrupted chloride transport to the phagolysosome [169,170]. Thus the CFTR mutation in CF results in impaired bacterial killing [171]. Moreover, CF neutrophils also demonstrate an increased capacity to release their primary granule contents such as MPO and neutrophil elastase (NE). The uncontrolled release of these enzymes causes lung tissue damage and severe airway inflammation. We have shown that P. aeruginosa LPS-induced MPO levels can be reduced by treatment with the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), plausibly by restoring the trafficking of ΔF508-CFTR, suggesting that a functional CFTR is required to keep a tab on uncontrolled neutrophil activation [172]. Mechanistically, an absence or dysfunction of CFTR in neutrophils results in the deactivation of the guanosine triphosphate (GTP)-binding protein Rab27a, which causes impaired granule exocytosis [168,172]. Several studies now agree that the pharmacological inhibition of CFTR or the mutant ΔF508-CFTR is sufficient to cause deregulated neutrophil activation via the activation of the NFκB pathway, resulting in hyperinflammation [172]."}

PMC:7565665 / 45809-47945 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7565665 / 45809-47945 JSON TXT