PMC:3359311 / 117-1955 JSONTXT

{"project":"bionlp-st-ge-2016-uniprot","denotations":[{"id":"T364","span":{"begin":171,"end":189},"obj":"P01584"},{"id":"T365","span":{"begin":191,"end":196},"obj":"P01584"},{"id":"T366","span":{"begin":263,"end":268},"obj":"P01584"},{"id":"T367","span":{"begin":354,"end":359},"obj":"P01584"},{"id":"T368","span":{"begin":452,"end":457},"obj":"P01584"},{"id":"T369","span":{"begin":640,"end":645},"obj":"P01584"},{"id":"T370","span":{"begin":894,"end":899},"obj":"P01584"},{"id":"T371","span":{"begin":1064,"end":1069},"obj":"P01584"},{"id":"T372","span":{"begin":1132,"end":1137},"obj":"P01584"},{"id":"T373","span":{"begin":1331,"end":1336},"obj":"P01584"},{"id":"T374","span":{"begin":1340,"end":1344},"obj":"P10145"},{"id":"T375","span":{"begin":1495,"end":1500},"obj":"P01584"},{"id":"T376","span":{"begin":1585,"end":1590},"obj":"P01584"},{"id":"T377","span":{"begin":1725,"end":1730},"obj":"P01584"}],"namespaces":[{"prefix":"_base","uri":"http://www.uniprot.org/uniprot/"}],"text":"Background\nInflammation and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.\n\nResults\nBronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.\n\nConclusion\nHematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function. "}

{"project":"bionlp-st-ge-2016-reference","denotations":[{"id":"T49","span":{"begin":590,"end":597},"obj":"Gene_expression"},{"id":"T50","span":{"begin":629,"end":639},"obj":"Positive_regulation"},{"id":"T40","span":{"begin":171,"end":189},"obj":"Protein"},{"id":"T41","span":{"begin":191,"end":196},"obj":"Protein"},{"id":"T42","span":{"begin":230,"end":239},"obj":"Localization"},{"id":"T43","span":{"begin":263,"end":268},"obj":"Protein"},{"id":"T44","span":{"begin":269,"end":277},"obj":"Regulation"},{"id":"T45","span":{"begin":354,"end":359},"obj":"Protein"},{"id":"T46","span":{"begin":443,"end":451},"obj":"Positive_regulation"},{"id":"T47","span":{"begin":452,"end":457},"obj":"Protein"},{"id":"T48","span":{"begin":458,"end":468},"obj":"Gene_expression"},{"id":"T51","span":{"begin":640,"end":645},"obj":"Protein"},{"id":"T52","span":{"begin":868,"end":876},"obj":"Gene_expression"},{"id":"T53","span":{"begin":894,"end":899},"obj":"Protein"},{"id":"T54","span":{"begin":944,"end":948},"obj":"Positive_regulation"},{"id":"T55","span":{"begin":1064,"end":1069},"obj":"Protein"},{"id":"T56","span":{"begin":1070,"end":1080},"obj":"Gene_expression"},{"id":"T57","span":{"begin":1086,"end":1096},"obj":"Positive_regulation"},{"id":"T58","span":{"begin":1132,"end":1137},"obj":"Protein"},{"id":"T59","span":{"begin":1325,"end":1330},"obj":"Regulation"},{"id":"T60","span":{"begin":1331,"end":1336},"obj":"Protein"},{"id":"T61","span":{"begin":1345,"end":1355},"obj":"Gene_expression"},{"id":"T62","span":{"begin":1356,"end":1370},"obj":"Positive_regulation"},{"id":"T63","span":{"begin":1470,"end":1477},"obj":"Positive_regulation"},{"id":"T64","span":{"begin":1495,"end":1500},"obj":"Protein"},{"id":"T65","span":{"begin":1547,"end":1556},"obj":"Positive_regulation"},{"id":"T66","span":{"begin":1585,"end":1590},"obj":"Protein"},{"id":"T67","span":{"begin":1591,"end":1600},"obj":"Localization"},{"id":"T68","span":{"begin":1715,"end":1724},"obj":"Positive_regulation"},{"id":"T69","span":{"begin":1724,"end":1730},"obj":"Protein"},{"id":"T70","span":{"begin":1731,"end":1741},"obj":"Gene_expression"},{"id":"T71","span":{"begin":1760,"end":1763},"obj":"Positive_regulation"}],"relations":[{"id":"R25","pred":"equivalentTo","subj":"T41","obj":"T40"},{"id":"R26","pred":"themeOf","subj":"T42","obj":"T44"},{"id":"R27","pred":"themeOf","subj":"T43","obj":"T42"},{"id":"R28","pred":"themeOf","subj":"T47","obj":"T48"},{"id":"R29","pred":"themeOf","subj":"T48","obj":"T46"},{"id":"R30","pred":"themeOf","subj":"T49","obj":"T50"},{"id":"R31","pred":"themeOf","subj":"T51","obj":"T49"},{"id":"R32","pred":"themeOf","subj":"T52","obj":"T54"},{"id":"R33","pred":"themeOf","subj":"T53","obj":"T52"},{"id":"R34","pred":"themeOf","subj":"T55","obj":"T56"},{"id":"R35","pred":"themeOf","subj":"T56","obj":"T57"},{"id":"R36","pred":"themeOf","subj":"T60","obj":"T61"},{"id":"R37","pred":"themeOf","subj":"T61","obj":"T62"},{"id":"R38","pred":"themeOf","subj":"T62","obj":"T59"},{"id":"R39","pred":"themeOf","subj":"T64","obj":"T63"},{"id":"R40","pred":"themeOf","subj":"T66","obj":"T67"},{"id":"R41","pred":"themeOf","subj":"T67","obj":"T65"},{"id":"R42","pred":"themeOf","subj":"T68","obj":"T71"},{"id":"R43","pred":"themeOf","subj":"T69","obj":"T70"},{"id":"R44","pred":"themeOf","subj":"T70","obj":"T68"}],"attributes":[{"id":"M6","pred":"Negation","subj":"T49","obj":"true"},{"id":"M8","pred":"Speculation","subj":"T71","obj":"true"},{"id":"M7","pred":"Negation","subj":"T59","obj":"true"},{"id":"M5","pred":"Speculation","subj":"T46","obj":"true"}],"namespaces":[{"prefix":"_base","uri":"http://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"Background\nInflammation and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.\n\nResults\nBronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.\n\nConclusion\nHematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function. "}

{"project":"bionlp-st-ge-2016-reference-tees","denotations":[{"id":"T802","span":{"begin":171,"end":189},"obj":"Protein"},{"id":"T803","span":{"begin":191,"end":196},"obj":"Protein"},{"id":"T804","span":{"begin":220,"end":228},"obj":"Positive_regulation"},{"id":"T805","span":{"begin":220,"end":228},"obj":"Positive_regulation"},{"id":"T806","span":{"begin":263,"end":268},"obj":"Protein"},{"id":"T807","span":{"begin":230,"end":239},"obj":"Localization"},{"id":"T808","span":{"begin":354,"end":359},"obj":"Protein"},{"id":"T809","span":{"begin":640,"end":645},"obj":"Protein"},{"id":"T810","span":{"begin":720,"end":729},"obj":"Protein"},{"id":"T811","span":{"begin":590,"end":597},"obj":"Gene_expression"},{"id":"T812","span":{"begin":709,"end":719},"obj":"Positive_regulation"},{"id":"T813","span":{"begin":894,"end":899},"obj":"Protein"},{"id":"T814","span":{"begin":925,"end":934},"obj":"Protein"},{"id":"T815","span":{"begin":868,"end":876},"obj":"Gene_expression"},{"id":"T816","span":{"begin":913,"end":924},"obj":"Positive_regulation"},{"id":"T817","span":{"begin":883,"end":890},"obj":"Positive_regulation"},{"id":"T818","span":{"begin":1039,"end":1048},"obj":"Protein"},{"id":"T819","span":{"begin":1064,"end":1069},"obj":"Protein"},{"id":"T820","span":{"begin":1049,"end":1059},"obj":"Positive_regulation"},{"id":"T821","span":{"begin":1070,"end":1080},"obj":"Gene_expression"},{"id":"T822","span":{"begin":1049,"end":1059},"obj":"Positive_regulation"},{"id":"T823","span":{"begin":1132,"end":1137},"obj":"Protein"},{"id":"T824","span":{"begin":1166,"end":1171},"obj":"Protein"},{"id":"T825","span":{"begin":1138,"end":1148},"obj":"Gene_expression"},{"id":"T826","span":{"begin":1153,"end":1162},"obj":"Positive_regulation"},{"id":"T827","span":{"begin":1194,"end":1202},"obj":"Positive_regulation"},{"id":"T828","span":{"begin":1256,"end":1260},"obj":"Protein"},{"id":"T829","span":{"begin":1331,"end":1336},"obj":"Protein"},{"id":"T830","span":{"begin":1340,"end":1344},"obj":"Protein"},{"id":"T831","span":{"begin":1242,"end":1252},"obj":"Negative_regulation"},{"id":"T832","span":{"begin":1345,"end":1355},"obj":"Gene_expression"},{"id":"T833","span":{"begin":1345,"end":1355},"obj":"Gene_expression"},{"id":"T834","span":{"begin":1325,"end":1330},"obj":"Positive_regulation"},{"id":"T835","span":{"begin":1325,"end":1330},"obj":"Positive_regulation"},{"id":"T836","span":{"begin":1495,"end":1500},"obj":"Protein"},{"id":"T837","span":{"begin":1585,"end":1590},"obj":"Protein"},{"id":"T838","span":{"begin":1626,"end":1660},"obj":"Protein"},{"id":"T839","span":{"begin":1591,"end":1600},"obj":"Localization"},{"id":"T840","span":{"begin":1591,"end":1600},"obj":"Localization"},{"id":"T841","span":{"begin":1725,"end":1730},"obj":"Protein"},{"id":"T842","span":{"begin":1792,"end":1797},"obj":"Protein"},{"id":"T843","span":{"begin":1823,"end":1827},"obj":"Protein"},{"id":"T844","span":{"begin":1731,"end":1741},"obj":"Gene_expression"},{"id":"T845","span":{"begin":1760,"end":1763},"obj":"Positive_regulation"},{"id":"T846","span":{"begin":1780,"end":1788},"obj":"Positive_regulation"},{"id":"T847","span":{"begin":1815,"end":1819},"obj":"Negative_regulation"},{"id":"T848","span":{"begin":1715,"end":1724},"obj":"Positive_regulation"}],"relations":[{"id":"R667","pred":"themeOf","subj":"T802","obj":"T804"},{"id":"R668","pred":"themeOf","subj":"T803","obj":"T805"},{"id":"R669","pred":"themeOf","subj":"T806","obj":"T807"},{"id":"R670","pred":"themeOf","subj":"T809","obj":"T811"},{"id":"R671","pred":"themeOf","subj":"T810","obj":"T812"},{"id":"R672","pred":"themeOf","subj":"T813","obj":"T815"},{"id":"R673","pred":"themeOf","subj":"T814","obj":"T816"},{"id":"R674","pred":"themeOf","subj":"T816","obj":"T817"},{"id":"R675","pred":"themeOf","subj":"T818","obj":"T820"},{"id":"R676","pred":"themeOf","subj":"T819","obj":"T821"},{"id":"R677","pred":"themeOf","subj":"T821","obj":"T822"},{"id":"R678","pred":"themeOf","subj":"T823","obj":"T825"},{"id":"R679","pred":"themeOf","subj":"T825","obj":"T826"},{"id":"R680","pred":"themeOf","subj":"T825","obj":"T827"},{"id":"R681","pred":"themeOf","subj":"T828","obj":"T831"},{"id":"R682","pred":"themeOf","subj":"T829","obj":"T832"},{"id":"R683","pred":"themeOf","subj":"T830","obj":"T833"},{"id":"R684","pred":"themeOf","subj":"T832","obj":"T834"},{"id":"R685","pred":"themeOf","subj":"T833","obj":"T835"},{"id":"R686","pred":"themeOf","subj":"T837","obj":"T839"},{"id":"R687","pred":"themeOf","subj":"T838","obj":"T840"},{"id":"R688","pred":"themeOf","subj":"T841","obj":"T844"},{"id":"R689","pred":"themeOf","subj":"T842","obj":"T846"},{"id":"R690","pred":"themeOf","subj":"T843","obj":"T847"},{"id":"R691","pred":"themeOf","subj":"T844","obj":"T845"},{"id":"R692","pred":"themeOf","subj":"T844","obj":"T848"}],"text":"Background\nInflammation and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.\n\nResults\nBronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.\n\nConclusion\nHematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function. "}

{"project":"events-check-again","denotations":[{"id":"T770","span":{"begin":171,"end":189},"obj":"Protein"},{"id":"T771","span":{"begin":191,"end":196},"obj":"Protein"},{"id":"T772","span":{"begin":230,"end":239},"obj":"Localization"},{"id":"T773","span":{"begin":263,"end":268},"obj":"Protein"},{"id":"T774","span":{"begin":269,"end":277},"obj":"Regulation"},{"id":"T775","span":{"begin":354,"end":359},"obj":"Protein"},{"id":"T776","span":{"begin":443,"end":451},"obj":"Positive_regulation"},{"id":"T777","span":{"begin":452,"end":457},"obj":"Protein"},{"id":"T778","span":{"begin":458,"end":468},"obj":"Gene_expression"},{"id":"T779","span":{"begin":590,"end":597},"obj":"Gene_expression"},{"id":"T780","span":{"begin":629,"end":639},"obj":"Positive_regulation"},{"id":"T781","span":{"begin":640,"end":645},"obj":"Protein"},{"id":"T782","span":{"begin":868,"end":876},"obj":"Gene_expression"},{"id":"T783","span":{"begin":894,"end":899},"obj":"Protein"},{"id":"T784","span":{"begin":944,"end":948},"obj":"Positive_regulation"},{"id":"T785","span":{"begin":1064,"end":1069},"obj":"Protein"},{"id":"T786","span":{"begin":1070,"end":1080},"obj":"Gene_expression"},{"id":"T787","span":{"begin":1086,"end":1096},"obj":"Positive_regulation"},{"id":"T788","span":{"begin":1132,"end":1137},"obj":"Protein"},{"id":"T789","span":{"begin":1325,"end":1330},"obj":"Regulation"},{"id":"T790","span":{"begin":1331,"end":1336},"obj":"Protein"},{"id":"T791","span":{"begin":1345,"end":1355},"obj":"Gene_expression"},{"id":"T792","span":{"begin":1356,"end":1370},"obj":"Positive_regulation"},{"id":"T793","span":{"begin":1470,"end":1477},"obj":"Positive_regulation"},{"id":"T794","span":{"begin":1495,"end":1500},"obj":"Protein"},{"id":"T795","span":{"begin":1547,"end":1556},"obj":"Positive_regulation"},{"id":"T796","span":{"begin":1585,"end":1590},"obj":"Protein"},{"id":"T797","span":{"begin":1591,"end":1600},"obj":"Localization"},{"id":"T798","span":{"begin":1715,"end":1724},"obj":"Positive_regulation"},{"id":"T799","span":{"begin":1724,"end":1730},"obj":"Protein"},{"id":"T800","span":{"begin":1731,"end":1741},"obj":"Gene_expression"},{"id":"T801","span":{"begin":1760,"end":1763},"obj":"Positive_regulation"}],"relations":[{"id":"R647","pred":"equivalentTo","subj":"T771","obj":"T770"},{"id":"R648","pred":"themeOf","subj":"T772","obj":"T774"},{"id":"R649","pred":"themeOf","subj":"T773","obj":"T772"},{"id":"R650","pred":"themeOf","subj":"T777","obj":"T778"},{"id":"R651","pred":"themeOf","subj":"T778","obj":"T776"},{"id":"R652","pred":"themeOf","subj":"T779","obj":"T780"},{"id":"R653","pred":"themeOf","subj":"T781","obj":"T779"},{"id":"R654","pred":"themeOf","subj":"T782","obj":"T784"},{"id":"R655","pred":"themeOf","subj":"T783","obj":"T782"},{"id":"R656","pred":"themeOf","subj":"T785","obj":"T786"},{"id":"R657","pred":"themeOf","subj":"T786","obj":"T787"},{"id":"R658","pred":"themeOf","subj":"T790","obj":"T791"},{"id":"R659","pred":"themeOf","subj":"T791","obj":"T792"},{"id":"R660","pred":"themeOf","subj":"T792","obj":"T789"},{"id":"R661","pred":"themeOf","subj":"T794","obj":"T793"},{"id":"R662","pred":"themeOf","subj":"T796","obj":"T797"},{"id":"R663","pred":"themeOf","subj":"T797","obj":"T795"},{"id":"R664","pred":"themeOf","subj":"T798","obj":"T801"},{"id":"R665","pred":"themeOf","subj":"T799","obj":"T800"},{"id":"R666","pred":"themeOf","subj":"T800","obj":"T798"}],"attributes":[{"id":"M20","pred":"Speculation","subj":"T801","obj":"true"},{"id":"M19","pred":"Negation","subj":"T789","obj":"true"},{"id":"M17","pred":"Speculation","subj":"T776","obj":"true"},{"id":"M18","pred":"Negation","subj":"T779","obj":"true"}],"text":"Background\nInflammation and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.\n\nResults\nBronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.\n\nConclusion\nHematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function. "}

{"project":"ICD10","denotations":[{"id":"T694","span":{"begin":149,"end":164},"obj":"http://purl.bioontology.org/ontology/ICD10/E84"},{"id":"T695","span":{"begin":149,"end":164},"obj":"http://purl.bioontology.org/ontology/ICD10/E84.9"}],"text":"Background\nInflammation and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.\n\nResults\nBronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.\n\nConclusion\nHematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function. "}

{"project":"GO-CC","denotations":[{"id":"T688","span":{"begin":496,"end":500},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T689","span":{"begin":565,"end":569},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T690","span":{"begin":672,"end":677},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T691","span":{"begin":812,"end":817},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T692","span":{"begin":1297,"end":1302},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T693","span":{"begin":1412,"end":1417},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"Background\nInflammation and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.\n\nResults\nBronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.\n\nConclusion\nHematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function. "}

{"project":"GO-MF","denotations":[{"id":"T696","span":{"begin":1340,"end":1344},"obj":"http://purl.obolibrary.org/obo/GO_0005153"}],"text":"Background\nInflammation and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.\n\nResults\nBronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.\n\nConclusion\nHematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function. "}

{"project":"GO-BP","denotations":[{"id":"T680","span":{"begin":11,"end":23},"obj":"http://purl.obolibrary.org/obo/GO_0006954"},{"id":"T681","span":{"begin":171,"end":189},"obj":"http://purl.obolibrary.org/obo/GO_0050720"},{"id":"T682","span":{"begin":171,"end":189},"obj":"http://purl.obolibrary.org/obo/GO_0050702"},{"id":"T683","span":{"begin":183,"end":193},"obj":"http://purl.obolibrary.org/obo/GO_0032611"},{"id":"T684","span":{"begin":230,"end":239},"obj":"http://purl.obolibrary.org/obo/GO_0046903"},{"id":"T685","span":{"begin":1591,"end":1600},"obj":"http://purl.obolibrary.org/obo/GO_0046903"},{"id":"T686","span":{"begin":1340,"end":1355},"obj":"http://purl.obolibrary.org/obo/GO_0032677"},{"id":"T687","span":{"begin":1340,"end":1355},"obj":"http://purl.obolibrary.org/obo/GO_0032637"}],"text":"Background\nInflammation and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.\n\nResults\nBronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.\n\nConclusion\nHematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function. "}

{"project":"UBERON-AE","denotations":[{"id":"T36","span":{"begin":794,"end":799},"obj":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"text":"Background\nInflammation and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.\n\nResults\nBronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.\n\nConclusion\nHematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function. "}

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and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.\n\nResults\nBronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.\n\nConclusion\nHematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function. "}

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and infection are major determinants of disease severity and consequently, the quality of life and outcome for patients with cystic fibrosis (CF). Interleukin-1 beta (IL-1β) is a key inflammatory mediator. Secretion of biologically active IL-1β involves inflammasome-mediated processing. Little is known about the contribution of IL-1β and the inflammasomes in CF inflammatory disease. This study examines inflammasome-mediated IL-1β production in CF bronchial epithelial cell lines and human patients with CF.\n\nResults\nBronchial epithelial cell lines were found to produce negligible amounts of basal or stimulated IL-1β compared to hematopoeitic cells and they did not significantly upregulate caspase-1 activity upon inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs) from both CF and healthy control subjects produced large amounts of IL-1β and strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from CF patients and controls displayed similar levels of caspase-1 activation and IL-1β production when stimulated with inflammasome activators. This IL-1β production was dependent on NF-κB activity and could be enhanced by priming with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP-1 cells did not significantly alter IL-1β or IL-8 production in response to P. aeruginosa.\n\nConclusion\nHematopoeitic cells appear to be the predominant source of inflammasome-induced pro-inflammatory IL-1β in CF. PBMCs derived from CF subjects display preserved inflammasome activation and IL-1β secretion in response to the major CF pathogen Pseudomonas aeruginosa. However, our data do not support the hypothesis that increased IL-1β production in CF subjects is due to an intrinsic increase in NF-κB activity through loss of CFTR function. "}

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