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test3

{"project":"test3","denotations":[{"id":"T908","span":{"begin":1407,"end":1412},"obj":"Protein"},{"id":"T907","span":{"begin":1376,"end":1383},"obj":"Positive_regulation"},{"id":"T906","span":{"begin":1371,"end":1375},"obj":"Protein"},{"id":"T905","span":{"begin":1360,"end":1365},"obj":"Protein"},{"id":"T904","span":{"begin":1351,"end":1359},"obj":"Regulation"},{"id":"T903","span":{"begin":502,"end":511},"obj":"Negative_regulation"},{"id":"T902","span":{"begin":411,"end":416},"obj":"Protein"},{"id":"T901","span":{"begin":396,"end":400},"obj":"Protein"},{"id":"T900","span":{"begin":370,"end":384},"obj":"Protein"},{"id":"T839","span":{"begin":1407,"end":1412},"obj":"Protein"},{"id":"T838","span":{"begin":1371,"end":1375},"obj":"Protein"},{"id":"T837","span":{"begin":1360,"end":1365},"obj":"Protein"},{"id":"T836","span":{"begin":411,"end":416},"obj":"Protein"},{"id":"T835","span":{"begin":396,"end":400},"obj":"Protein"},{"id":"T834","span":{"begin":370,"end":384},"obj":"Protein"}],"relations":[{"id":"R549","pred":"causeOf","subj":"T905","obj":"T907"},{"id":"R550","pred":"causeOf","subj":"T906","obj":"T907"},{"id":"R551","pred":"themeOf","subj":"T907","obj":"T904"}],"text":"A20 is an ubiquitin-editing enzyme belonging to the OTU-domain family of DUBs. Interestingly, A20 also harbors atypical zinc finger dependent K48-specific E3 ubiquitin ligase activity. Both catalytic and noncatalytic mechanisms were previously shown to be involved in the negative regulation of proinflammatory signaling by A20 in response to multiple receptors such as TNF receptor I [37]–[39], TLR4 [40], and IL-1R [41]. The anti-inflammatory role of A20 is clearly demonstrated by the fact that A20 deficient mice die early after birth due to severe multi-organ inflammation and cachexia [37]. More recently, gene targeting of A20 in specific cell types was shown to be associated with autoimmunity and chronic inflammation [42]–[48], further illustrating that A20 is an important brake on the inflammatory response. The relevance of these findings for human disease has recently been illustrated through the identification of polymorphisms in the A20 locus that are associated with several autoimmune diseases and chronic inflammation [45]. In contrast to its well established function in the regulation of proinflammatory responses, the role of A20 in the regulation of antiviral immune responses is less well described and limited to a number of in vitro studies using overexpression or silencing in specific cell lines, indicating that A20 may regulate RIG-I- and TLR3-induced signaling to NF-κB and IRF-3 [49]–[52]. However, the precise in vivo role of A20 in the response to viral infection remains to be clarified. Using myeloid cell specific A20 knockout mice (A20myel-KO) that were recently generated in our lab and primary cells derived of these mice, we here provide evidence that A20 is a crucial negative regulator of IAV-induced proinflammatory and antiviral signaling in macrophages. Interestingly, A20myel-KO mice show enhanced survival and reduced morbidity in response to IAV lung infection compared to wild type mice. Protection against IAV in A20myel-KO mice is associated with increased cytokine and chemokine production, augmented recruitment of innate immune cells such as neutophils and alveolar macrophages, and enhanced viral clearance. These results suggest that boosting the innate immune response to IAV by targeting A20 activity in myeloid cells might have therapeutic potential."}

2_test

{"project":"2_test","denotations":[{"id":"22396652-11009421-98461837","span":{"begin":386,"end":388},"obj":"11009421"},{"id":"22396652-22099304-98461838","span":{"begin":391,"end":393},"obj":"22099304"},{"id":"22396652-15334086-98461839","span":{"begin":402,"end":404},"obj":"15334086"},{"id":"22396652-20185725-98461840","span":{"begin":418,"end":420},"obj":"20185725"},{"id":"22396652-11009421-98461841","span":{"begin":592,"end":594},"obj":"11009421"},{"id":"22396652-22019834-98461842","span":{"begin":728,"end":730},"obj":"22019834"},{"id":"22396652-21841782-98461843","span":{"begin":733,"end":735},"obj":"21841782"},{"id":"22396652-19643665-98461844","span":{"begin":1040,"end":1042},"obj":"19643665"},{"id":"22396652-16765340-98461845","span":{"begin":1414,"end":1416},"obj":"16765340"},{"id":"22396652-15661910-98461846","span":{"begin":1419,"end":1421},"obj":"15661910"}],"text":"A20 is an ubiquitin-editing enzyme belonging to the OTU-domain family of DUBs. Interestingly, A20 also harbors atypical zinc finger dependent K48-specific E3 ubiquitin ligase activity. Both catalytic and noncatalytic mechanisms were previously shown to be involved in the negative regulation of proinflammatory signaling by A20 in response to multiple receptors such as TNF receptor I [37]–[39], TLR4 [40], and IL-1R [41]. The anti-inflammatory role of A20 is clearly demonstrated by the fact that A20 deficient mice die early after birth due to severe multi-organ inflammation and cachexia [37]. More recently, gene targeting of A20 in specific cell types was shown to be associated with autoimmunity and chronic inflammation [42]–[48], further illustrating that A20 is an important brake on the inflammatory response. The relevance of these findings for human disease has recently been illustrated through the identification of polymorphisms in the A20 locus that are associated with several autoimmune diseases and chronic inflammation [45]. In contrast to its well established function in the regulation of proinflammatory responses, the role of A20 in the regulation of antiviral immune responses is less well described and limited to a number of in vitro studies using overexpression or silencing in specific cell lines, indicating that A20 may regulate RIG-I- and TLR3-induced signaling to NF-κB and IRF-3 [49]–[52]. However, the precise in vivo role of A20 in the response to viral infection remains to be clarified. Using myeloid cell specific A20 knockout mice (A20myel-KO) that were recently generated in our lab and primary cells derived of these mice, we here provide evidence that A20 is a crucial negative regulator of IAV-induced proinflammatory and antiviral signaling in macrophages. Interestingly, A20myel-KO mice show enhanced survival and reduced morbidity in response to IAV lung infection compared to wild type mice. Protection against IAV in A20myel-KO mice is associated with increased cytokine and chemokine production, augmented recruitment of innate immune cells such as neutophils and alveolar macrophages, and enhanced viral clearance. These results suggest that boosting the innate immune response to IAV by targeting A20 activity in myeloid cells might have therapeutic potential."}

pmc-enju-pas

bionlp-st-ge-2016-test-proteins

{"project":"bionlp-st-ge-2016-test-proteins","denotations":[{"id":"T1085","span":{"begin":1407,"end":1412},"obj":"Protein"},{"id":"T1084","span":{"begin":1371,"end":1375},"obj":"Protein"},{"id":"T1083","span":{"begin":1360,"end":1365},"obj":"Protein"},{"id":"T1082","span":{"begin":411,"end":416},"obj":"Protein"},{"id":"T1081","span":{"begin":396,"end":400},"obj":"Protein"},{"id":"T1080","span":{"begin":370,"end":384},"obj":"Protein"}],"namespaces":[{"prefix":"_base","uri":"http://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"A20 is an ubiquitin-editing enzyme belonging to the OTU-domain family of DUBs. Interestingly, A20 also harbors atypical zinc finger dependent K48-specific E3 ubiquitin ligase activity. Both catalytic and noncatalytic mechanisms were previously shown to be involved in the negative regulation of proinflammatory signaling by A20 in response to multiple receptors such as TNF receptor I [37]–[39], TLR4 [40], and IL-1R [41]. The anti-inflammatory role of A20 is clearly demonstrated by the fact that A20 deficient mice die early after birth due to severe multi-organ inflammation and cachexia [37]. More recently, gene targeting of A20 in specific cell types was shown to be associated with autoimmunity and chronic inflammation [42]–[48], further illustrating that A20 is an important brake on the inflammatory response. The relevance of these findings for human disease has recently been illustrated through the identification of polymorphisms in the A20 locus that are associated with several autoimmune diseases and chronic inflammation [45]. In contrast to its well established function in the regulation of proinflammatory responses, the role of A20 in the regulation of antiviral immune responses is less well described and limited to a number of in vitro studies using overexpression or silencing in specific cell lines, indicating that A20 may regulate RIG-I- and TLR3-induced signaling to NF-κB and IRF-3 [49]–[52]. However, the precise in vivo role of A20 in the response to viral infection remains to be clarified. Using myeloid cell specific A20 knockout mice (A20myel-KO) that were recently generated in our lab and primary cells derived of these mice, we here provide evidence that A20 is a crucial negative regulator of IAV-induced proinflammatory and antiviral signaling in macrophages. Interestingly, A20myel-KO mice show enhanced survival and reduced morbidity in response to IAV lung infection compared to wild type mice. Protection against IAV in A20myel-KO mice is associated with increased cytokine and chemokine production, augmented recruitment of innate immune cells such as neutophils and alveolar macrophages, and enhanced viral clearance. These results suggest that boosting the innate immune response to IAV by targeting A20 activity in myeloid cells might have therapeutic potential."}

bionlp-st-ge-2016-uniprot

UBERON-AE

{"project":"UBERON-AE","denotations":[{"id":"T910","span":{"begin":1897,"end":1901},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T909","span":{"begin":559,"end":564},"obj":"http://purl.obolibrary.org/obo/UBERON_0000062"}],"text":"A20 is an ubiquitin-editing enzyme belonging to the OTU-domain family of DUBs. Interestingly, A20 also harbors atypical zinc finger dependent K48-specific E3 ubiquitin ligase activity. Both catalytic and noncatalytic mechanisms were previously shown to be involved in the negative regulation of proinflammatory signaling by A20 in response to multiple receptors such as TNF receptor I [37]–[39], TLR4 [40], and IL-1R [41]. The anti-inflammatory role of A20 is clearly demonstrated by the fact that A20 deficient mice die early after birth due to severe multi-organ inflammation and cachexia [37]. More recently, gene targeting of A20 in specific cell types was shown to be associated with autoimmunity and chronic inflammation [42]–[48], further illustrating that A20 is an important brake on the inflammatory response. The relevance of these findings for human disease has recently been illustrated through the identification of polymorphisms in the A20 locus that are associated with several autoimmune diseases and chronic inflammation [45]. In contrast to its well established function in the regulation of proinflammatory responses, the role of A20 in the regulation of antiviral immune responses is less well described and limited to a number of in vitro studies using overexpression or silencing in specific cell lines, indicating that A20 may regulate RIG-I- and TLR3-induced signaling to NF-κB and IRF-3 [49]–[52]. However, the precise in vivo role of A20 in the response to viral infection remains to be clarified. Using myeloid cell specific A20 knockout mice (A20myel-KO) that were recently generated in our lab and primary cells derived of these mice, we here provide evidence that A20 is a crucial negative regulator of IAV-induced proinflammatory and antiviral signaling in macrophages. Interestingly, A20myel-KO mice show enhanced survival and reduced morbidity in response to IAV lung infection compared to wild type mice. Protection against IAV in A20myel-KO mice is associated with increased cytokine and chemokine production, augmented recruitment of innate immune cells such as neutophils and alveolar macrophages, and enhanced viral clearance. These results suggest that boosting the innate immune response to IAV by targeting A20 activity in myeloid cells might have therapeutic potential."}

GO-BP

GO-MF

GO-CC

{"project":"GO-CC","denotations":[{"id":"T1215","span":{"begin":2273,"end":2278},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1214","span":{"begin":2085,"end":2090},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1213","span":{"begin":1636,"end":1641},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1212","span":{"begin":1539,"end":1543},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1211","span":{"begin":1315,"end":1319},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1210","span":{"begin":646,"end":650},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"A20 is an ubiquitin-editing enzyme belonging to the OTU-domain family of DUBs. Interestingly, A20 also harbors atypical zinc finger dependent K48-specific E3 ubiquitin ligase activity. Both catalytic and noncatalytic mechanisms were previously shown to be involved in the negative regulation of proinflammatory signaling by A20 in response to multiple receptors such as TNF receptor I [37]–[39], TLR4 [40], and IL-1R [41]. The anti-inflammatory role of A20 is clearly demonstrated by the fact that A20 deficient mice die early after birth due to severe multi-organ inflammation and cachexia [37]. More recently, gene targeting of A20 in specific cell types was shown to be associated with autoimmunity and chronic inflammation [42]–[48], further illustrating that A20 is an important brake on the inflammatory response. The relevance of these findings for human disease has recently been illustrated through the identification of polymorphisms in the A20 locus that are associated with several autoimmune diseases and chronic inflammation [45]. In contrast to its well established function in the regulation of proinflammatory responses, the role of A20 in the regulation of antiviral immune responses is less well described and limited to a number of in vitro studies using overexpression or silencing in specific cell lines, indicating that A20 may regulate RIG-I- and TLR3-induced signaling to NF-κB and IRF-3 [49]–[52]. However, the precise in vivo role of A20 in the response to viral infection remains to be clarified. Using myeloid cell specific A20 knockout mice (A20myel-KO) that were recently generated in our lab and primary cells derived of these mice, we here provide evidence that A20 is a crucial negative regulator of IAV-induced proinflammatory and antiviral signaling in macrophages. Interestingly, A20myel-KO mice show enhanced survival and reduced morbidity in response to IAV lung infection compared to wild type mice. Protection against IAV in A20myel-KO mice is associated with increased cytokine and chemokine production, augmented recruitment of innate immune cells such as neutophils and alveolar macrophages, and enhanced viral clearance. These results suggest that boosting the innate immune response to IAV by targeting A20 activity in myeloid cells might have therapeutic potential."}

sentences

{"project":"sentences","denotations":[{"id":"T945","span":{"begin":2166,"end":2312},"obj":"Sentence"},{"id":"T944","span":{"begin":1940,"end":2165},"obj":"Sentence"},{"id":"T943","span":{"begin":1802,"end":1939},"obj":"Sentence"},{"id":"T942","span":{"begin":1525,"end":1801},"obj":"Sentence"},{"id":"T941","span":{"begin":1424,"end":1524},"obj":"Sentence"},{"id":"T940","span":{"begin":1045,"end":1423},"obj":"Sentence"},{"id":"T939","span":{"begin":820,"end":1044},"obj":"Sentence"},{"id":"T938","span":{"begin":597,"end":819},"obj":"Sentence"},{"id":"T937","span":{"begin":423,"end":596},"obj":"Sentence"},{"id":"T936","span":{"begin":185,"end":422},"obj":"Sentence"},{"id":"T935","span":{"begin":79,"end":184},"obj":"Sentence"},{"id":"T934","span":{"begin":0,"end":78},"obj":"Sentence"},{"id":"T45","span":{"begin":0,"end":78},"obj":"Sentence"},{"id":"T46","span":{"begin":79,"end":184},"obj":"Sentence"},{"id":"T47","span":{"begin":185,"end":422},"obj":"Sentence"},{"id":"T48","span":{"begin":423,"end":596},"obj":"Sentence"},{"id":"T49","span":{"begin":597,"end":819},"obj":"Sentence"},{"id":"T50","span":{"begin":820,"end":1044},"obj":"Sentence"},{"id":"T51","span":{"begin":1045,"end":1423},"obj":"Sentence"},{"id":"T52","span":{"begin":1424,"end":1524},"obj":"Sentence"},{"id":"T53","span":{"begin":1525,"end":1801},"obj":"Sentence"},{"id":"T54","span":{"begin":1802,"end":1939},"obj":"Sentence"},{"id":"T55","span":{"begin":1940,"end":2165},"obj":"Sentence"},{"id":"T56","span":{"begin":2166,"end":2312},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"A20 is an ubiquitin-editing enzyme belonging to the OTU-domain family of DUBs. Interestingly, A20 also harbors atypical zinc finger dependent K48-specific E3 ubiquitin ligase activity. Both catalytic and noncatalytic mechanisms were previously shown to be involved in the negative regulation of proinflammatory signaling by A20 in response to multiple receptors such as TNF receptor I [37]–[39], TLR4 [40], and IL-1R [41]. The anti-inflammatory role of A20 is clearly demonstrated by the fact that A20 deficient mice die early after birth due to severe multi-organ inflammation and cachexia [37]. More recently, gene targeting of A20 in specific cell types was shown to be associated with autoimmunity and chronic inflammation [42]–[48], further illustrating that A20 is an important brake on the inflammatory response. The relevance of these findings for human disease has recently been illustrated through the identification of polymorphisms in the A20 locus that are associated with several autoimmune diseases and chronic inflammation [45]. In contrast to its well established function in the regulation of proinflammatory responses, the role of A20 in the regulation of antiviral immune responses is less well described and limited to a number of in vitro studies using overexpression or silencing in specific cell lines, indicating that A20 may regulate RIG-I- and TLR3-induced signaling to NF-κB and IRF-3 [49]–[52]. However, the precise in vivo role of A20 in the response to viral infection remains to be clarified. Using myeloid cell specific A20 knockout mice (A20myel-KO) that were recently generated in our lab and primary cells derived of these mice, we here provide evidence that A20 is a crucial negative regulator of IAV-induced proinflammatory and antiviral signaling in macrophages. Interestingly, A20myel-KO mice show enhanced survival and reduced morbidity in response to IAV lung infection compared to wild type mice. Protection against IAV in A20myel-KO mice is associated with increased cytokine and chemokine production, augmented recruitment of innate immune cells such as neutophils and alveolar macrophages, and enhanced viral clearance. These results suggest that boosting the innate immune response to IAV by targeting A20 activity in myeloid cells might have therapeutic potential."}

ICD10

{"project":"ICD10","denotations":[{"id":"T1166","span":{"begin":1484,"end":1499},"obj":"http://purl.bioontology.org/ontology/ICD10/B34.9"},{"id":"T1165","span":{"begin":582,"end":590},"obj":"http://purl.bioontology.org/ontology/ICD10/R64"}],"text":"A20 is an ubiquitin-editing enzyme belonging to the OTU-domain family of DUBs. Interestingly, A20 also harbors atypical zinc finger dependent K48-specific E3 ubiquitin ligase activity. Both catalytic and noncatalytic mechanisms were previously shown to be involved in the negative regulation of proinflammatory signaling by A20 in response to multiple receptors such as TNF receptor I [37]–[39], TLR4 [40], and IL-1R [41]. The anti-inflammatory role of A20 is clearly demonstrated by the fact that A20 deficient mice die early after birth due to severe multi-organ inflammation and cachexia [37]. More recently, gene targeting of A20 in specific cell types was shown to be associated with autoimmunity and chronic inflammation [42]–[48], further illustrating that A20 is an important brake on the inflammatory response. The relevance of these findings for human disease has recently been illustrated through the identification of polymorphisms in the A20 locus that are associated with several autoimmune diseases and chronic inflammation [45]. In contrast to its well established function in the regulation of proinflammatory responses, the role of A20 in the regulation of antiviral immune responses is less well described and limited to a number of in vitro studies using overexpression or silencing in specific cell lines, indicating that A20 may regulate RIG-I- and TLR3-induced signaling to NF-κB and IRF-3 [49]–[52]. However, the precise in vivo role of A20 in the response to viral infection remains to be clarified. Using myeloid cell specific A20 knockout mice (A20myel-KO) that were recently generated in our lab and primary cells derived of these mice, we here provide evidence that A20 is a crucial negative regulator of IAV-induced proinflammatory and antiviral signaling in macrophages. Interestingly, A20myel-KO mice show enhanced survival and reduced morbidity in response to IAV lung infection compared to wild type mice. Protection against IAV in A20myel-KO mice is associated with increased cytokine and chemokine production, augmented recruitment of innate immune cells such as neutophils and alveolar macrophages, and enhanced viral clearance. These results suggest that boosting the innate immune response to IAV by targeting A20 activity in myeloid cells might have therapeutic potential."}

simple1

{"project":"simple1","denotations":[{"id":"T1338","span":{"begin":1407,"end":1412},"obj":"Protein"},{"id":"T1337","span":{"begin":1371,"end":1375},"obj":"Protein"},{"id":"T1336","span":{"begin":1360,"end":1365},"obj":"Protein"},{"id":"T1335","span":{"begin":411,"end":416},"obj":"Protein"},{"id":"T1334","span":{"begin":396,"end":400},"obj":"Protein"},{"id":"T1333","span":{"begin":370,"end":384},"obj":"Protein"}],"text":"A20 is an ubiquitin-editing enzyme belonging to the OTU-domain family of DUBs. Interestingly, A20 also harbors atypical zinc finger dependent K48-specific E3 ubiquitin ligase activity. Both catalytic and noncatalytic mechanisms were previously shown to be involved in the negative regulation of proinflammatory signaling by A20 in response to multiple receptors such as TNF receptor I [37]–[39], TLR4 [40], and IL-1R [41]. The anti-inflammatory role of A20 is clearly demonstrated by the fact that A20 deficient mice die early after birth due to severe multi-organ inflammation and cachexia [37]. More recently, gene targeting of A20 in specific cell types was shown to be associated with autoimmunity and chronic inflammation [42]–[48], further illustrating that A20 is an important brake on the inflammatory response. The relevance of these findings for human disease has recently been illustrated through the identification of polymorphisms in the A20 locus that are associated with several autoimmune diseases and chronic inflammation [45]. In contrast to its well established function in the regulation of proinflammatory responses, the role of A20 in the regulation of antiviral immune responses is less well described and limited to a number of in vitro studies using overexpression or silencing in specific cell lines, indicating that A20 may regulate RIG-I- and TLR3-induced signaling to NF-κB and IRF-3 [49]–[52]. However, the precise in vivo role of A20 in the response to viral infection remains to be clarified. Using myeloid cell specific A20 knockout mice (A20myel-KO) that were recently generated in our lab and primary cells derived of these mice, we here provide evidence that A20 is a crucial negative regulator of IAV-induced proinflammatory and antiviral signaling in macrophages. Interestingly, A20myel-KO mice show enhanced survival and reduced morbidity in response to IAV lung infection compared to wild type mice. Protection against IAV in A20myel-KO mice is associated with increased cytokine and chemokine production, augmented recruitment of innate immune cells such as neutophils and alveolar macrophages, and enhanced viral clearance. These results suggest that boosting the innate immune response to IAV by targeting A20 activity in myeloid cells might have therapeutic potential."}

BioNLP16_DUT

{"project":"BioNLP16_DUT","denotations":[{"id":"T4149","span":{"begin":1407,"end":1412},"obj":"Protein"},{"id":"T4148","span":{"begin":1371,"end":1375},"obj":"Protein"},{"id":"T4147","span":{"begin":1360,"end":1365},"obj":"Protein"},{"id":"T4146","span":{"begin":411,"end":416},"obj":"Protein"},{"id":"T4145","span":{"begin":396,"end":400},"obj":"Protein"},{"id":"T4144","span":{"begin":370,"end":384},"obj":"Protein"}],"text":"A20 is an ubiquitin-editing enzyme belonging to the OTU-domain family of DUBs. Interestingly, A20 also harbors atypical zinc finger dependent K48-specific E3 ubiquitin ligase activity. Both catalytic and noncatalytic mechanisms were previously shown to be involved in the negative regulation of proinflammatory signaling by A20 in response to multiple receptors such as TNF receptor I [37]–[39], TLR4 [40], and IL-1R [41]. The anti-inflammatory role of A20 is clearly demonstrated by the fact that A20 deficient mice die early after birth due to severe multi-organ inflammation and cachexia [37]. More recently, gene targeting of A20 in specific cell types was shown to be associated with autoimmunity and chronic inflammation [42]–[48], further illustrating that A20 is an important brake on the inflammatory response. The relevance of these findings for human disease has recently been illustrated through the identification of polymorphisms in the A20 locus that are associated with several autoimmune diseases and chronic inflammation [45]. In contrast to its well established function in the regulation of proinflammatory responses, the role of A20 in the regulation of antiviral immune responses is less well described and limited to a number of in vitro studies using overexpression or silencing in specific cell lines, indicating that A20 may regulate RIG-I- and TLR3-induced signaling to NF-κB and IRF-3 [49]–[52]. However, the precise in vivo role of A20 in the response to viral infection remains to be clarified. Using myeloid cell specific A20 knockout mice (A20myel-KO) that were recently generated in our lab and primary cells derived of these mice, we here provide evidence that A20 is a crucial negative regulator of IAV-induced proinflammatory and antiviral signaling in macrophages. Interestingly, A20myel-KO mice show enhanced survival and reduced morbidity in response to IAV lung infection compared to wild type mice. Protection against IAV in A20myel-KO mice is associated with increased cytokine and chemokine production, augmented recruitment of innate immune cells such as neutophils and alveolar macrophages, and enhanced viral clearance. These results suggest that boosting the innate immune response to IAV by targeting A20 activity in myeloid cells might have therapeutic potential."}

BioNLP16_Messiy

{"project":"BioNLP16_Messiy","denotations":[{"id":"T3738","span":{"begin":1407,"end":1412},"obj":"Protein"},{"id":"T3737","span":{"begin":1371,"end":1375},"obj":"Protein"},{"id":"T3736","span":{"begin":1360,"end":1365},"obj":"Protein"},{"id":"T3735","span":{"begin":411,"end":416},"obj":"Protein"},{"id":"T3734","span":{"begin":396,"end":400},"obj":"Protein"},{"id":"T3733","span":{"begin":370,"end":384},"obj":"Protein"}],"text":"A20 is an ubiquitin-editing enzyme belonging to the OTU-domain family of DUBs. Interestingly, A20 also harbors atypical zinc finger dependent K48-specific E3 ubiquitin ligase activity. Both catalytic and noncatalytic mechanisms were previously shown to be involved in the negative regulation of proinflammatory signaling by A20 in response to multiple receptors such as TNF receptor I [37]–[39], TLR4 [40], and IL-1R [41]. The anti-inflammatory role of A20 is clearly demonstrated by the fact that A20 deficient mice die early after birth due to severe multi-organ inflammation and cachexia [37]. More recently, gene targeting of A20 in specific cell types was shown to be associated with autoimmunity and chronic inflammation [42]–[48], further illustrating that A20 is an important brake on the inflammatory response. The relevance of these findings for human disease has recently been illustrated through the identification of polymorphisms in the A20 locus that are associated with several autoimmune diseases and chronic inflammation [45]. In contrast to its well established function in the regulation of proinflammatory responses, the role of A20 in the regulation of antiviral immune responses is less well described and limited to a number of in vitro studies using overexpression or silencing in specific cell lines, indicating that A20 may regulate RIG-I- and TLR3-induced signaling to NF-κB and IRF-3 [49]–[52]. However, the precise in vivo role of A20 in the response to viral infection remains to be clarified. Using myeloid cell specific A20 knockout mice (A20myel-KO) that were recently generated in our lab and primary cells derived of these mice, we here provide evidence that A20 is a crucial negative regulator of IAV-induced proinflammatory and antiviral signaling in macrophages. Interestingly, A20myel-KO mice show enhanced survival and reduced morbidity in response to IAV lung infection compared to wild type mice. Protection against IAV in A20myel-KO mice is associated with increased cytokine and chemokine production, augmented recruitment of innate immune cells such as neutophils and alveolar macrophages, and enhanced viral clearance. These results suggest that boosting the innate immune response to IAV by targeting A20 activity in myeloid cells might have therapeutic potential."}

DLUT931

{"project":"DLUT931","denotations":[{"id":"T3821","span":{"begin":1351,"end":1359},"obj":"Regulation"},{"id":"T3806","span":{"begin":1407,"end":1412},"obj":"Protein"},{"id":"T3805","span":{"begin":1371,"end":1375},"obj":"Protein"},{"id":"T3804","span":{"begin":1360,"end":1365},"obj":"Protein"},{"id":"T3803","span":{"begin":411,"end":416},"obj":"Protein"},{"id":"T3802","span":{"begin":396,"end":400},"obj":"Protein"},{"id":"T3801","span":{"begin":370,"end":384},"obj":"Protein"}],"relations":[{"id":"R2970","pred":"themeOf","subj":"T3804","obj":"T3821"},{"id":"R2972","pred":"causeOf","subj":"T3806","obj":"T3821"}],"text":"A20 is an ubiquitin-editing enzyme belonging to the OTU-domain family of DUBs. Interestingly, A20 also harbors atypical zinc finger dependent K48-specific E3 ubiquitin ligase activity. Both catalytic and noncatalytic mechanisms were previously shown to be involved in the negative regulation of proinflammatory signaling by A20 in response to multiple receptors such as TNF receptor I [37]–[39], TLR4 [40], and IL-1R [41]. The anti-inflammatory role of A20 is clearly demonstrated by the fact that A20 deficient mice die early after birth due to severe multi-organ inflammation and cachexia [37]. More recently, gene targeting of A20 in specific cell types was shown to be associated with autoimmunity and chronic inflammation [42]–[48], further illustrating that A20 is an important brake on the inflammatory response. The relevance of these findings for human disease has recently been illustrated through the identification of polymorphisms in the A20 locus that are associated with several autoimmune diseases and chronic inflammation [45]. In contrast to its well established function in the regulation of proinflammatory responses, the role of A20 in the regulation of antiviral immune responses is less well described and limited to a number of in vitro studies using overexpression or silencing in specific cell lines, indicating that A20 may regulate RIG-I- and TLR3-induced signaling to NF-κB and IRF-3 [49]–[52]. However, the precise in vivo role of A20 in the response to viral infection remains to be clarified. Using myeloid cell specific A20 knockout mice (A20myel-KO) that were recently generated in our lab and primary cells derived of these mice, we here provide evidence that A20 is a crucial negative regulator of IAV-induced proinflammatory and antiviral signaling in macrophages. Interestingly, A20myel-KO mice show enhanced survival and reduced morbidity in response to IAV lung infection compared to wild type mice. Protection against IAV in A20myel-KO mice is associated with increased cytokine and chemokine production, augmented recruitment of innate immune cells such as neutophils and alveolar macrophages, and enhanced viral clearance. These results suggest that boosting the innate immune response to IAV by targeting A20 activity in myeloid cells might have therapeutic potential."}

bionlp-st-ge-2016-test-ihmc

bionlp-st-ge-2016-spacy-parsed

bionlp-st-ge-2016-test-tees

{"project":"bionlp-st-ge-2016-test-tees","denotations":[{"id":"T3988","span":{"begin":2249,"end":2252},"obj":"Protein"},{"id":"T3987","span":{"begin":1695,"end":1698},"obj":"Protein"},{"id":"T3986","span":{"begin":1461,"end":1464},"obj":"Protein"},{"id":"T3985","span":{"begin":1407,"end":1412},"obj":"Protein"},{"id":"T3984","span":{"begin":1397,"end":1402},"obj":"Protein"},{"id":"T3983","span":{"begin":1371,"end":1375},"obj":"Protein"},{"id":"T3982","span":{"begin":1343,"end":1346},"obj":"Protein"},{"id":"T3981","span":{"begin":1150,"end":1153},"obj":"Protein"},{"id":"T3980","span":{"begin":951,"end":960},"obj":"Protein"},{"id":"T3979","span":{"begin":764,"end":767},"obj":"Protein"},{"id":"T3978","span":{"begin":630,"end":633},"obj":"Protein"},{"id":"T3977","span":{"begin":453,"end":456},"obj":"Protein"},{"id":"T3976","span":{"begin":370,"end":384},"obj":"Protein"},{"id":"T3975","span":{"begin":324,"end":327},"obj":"Protein"},{"id":"T3974","span":{"begin":158,"end":174},"obj":"Protein"},{"id":"T3973","span":{"begin":155,"end":157},"obj":"Protein"},{"id":"T3972","span":{"begin":94,"end":97},"obj":"Protein"},{"id":"T3971","span":{"begin":52,"end":69},"obj":"Protein"},{"id":"T3970","span":{"begin":10,"end":19},"obj":"Protein"},{"id":"T3969","span":{"begin":0,"end":3},"obj":"Protein"}],"text":"A20 is an ubiquitin-editing enzyme belonging to the OTU-domain family of DUBs. Interestingly, A20 also harbors atypical zinc finger dependent K48-specific E3 ubiquitin ligase activity. Both catalytic and noncatalytic mechanisms were previously shown to be involved in the negative regulation of proinflammatory signaling by A20 in response to multiple receptors such as TNF receptor I [37]–[39], TLR4 [40], and IL-1R [41]. The anti-inflammatory role of A20 is clearly demonstrated by the fact that A20 deficient mice die early after birth due to severe multi-organ inflammation and cachexia [37]. More recently, gene targeting of A20 in specific cell types was shown to be associated with autoimmunity and chronic inflammation [42]–[48], further illustrating that A20 is an important brake on the inflammatory response. The relevance of these findings for human disease has recently been illustrated through the identification of polymorphisms in the A20 locus that are associated with several autoimmune diseases and chronic inflammation [45]. In contrast to its well established function in the regulation of proinflammatory responses, the role of A20 in the regulation of antiviral immune responses is less well described and limited to a number of in vitro studies using overexpression or silencing in specific cell lines, indicating that A20 may regulate RIG-I- and TLR3-induced signaling to NF-κB and IRF-3 [49]–[52]. However, the precise in vivo role of A20 in the response to viral infection remains to be clarified. Using myeloid cell specific A20 knockout mice (A20myel-KO) that were recently generated in our lab and primary cells derived of these mice, we here provide evidence that A20 is a crucial negative regulator of IAV-induced proinflammatory and antiviral signaling in macrophages. Interestingly, A20myel-KO mice show enhanced survival and reduced morbidity in response to IAV lung infection compared to wild type mice. Protection against IAV in A20myel-KO mice is associated with increased cytokine and chemokine production, augmented recruitment of innate immune cells such as neutophils and alveolar macrophages, and enhanced viral clearance. These results suggest that boosting the innate immune response to IAV by targeting A20 activity in myeloid cells might have therapeutic potential."}

testone

{"project":"testone","denotations":[{"id":"T783","span":{"begin":502,"end":511},"obj":"Negative_regulation"},{"id":"T771","span":{"begin":1407,"end":1412},"obj":"Protein"},{"id":"T770","span":{"begin":1371,"end":1375},"obj":"Protein"},{"id":"T769","span":{"begin":1360,"end":1365},"obj":"Protein"},{"id":"T768","span":{"begin":411,"end":416},"obj":"Protein"},{"id":"T767","span":{"begin":396,"end":400},"obj":"Protein"},{"id":"T766","span":{"begin":370,"end":384},"obj":"Protein"}],"text":"A20 is an ubiquitin-editing enzyme belonging to the OTU-domain family of DUBs. Interestingly, A20 also harbors atypical zinc finger dependent K48-specific E3 ubiquitin ligase activity. Both catalytic and noncatalytic mechanisms were previously shown to be involved in the negative regulation of proinflammatory signaling by A20 in response to multiple receptors such as TNF receptor I [37]–[39], TLR4 [40], and IL-1R [41]. The anti-inflammatory role of A20 is clearly demonstrated by the fact that A20 deficient mice die early after birth due to severe multi-organ inflammation and cachexia [37]. More recently, gene targeting of A20 in specific cell types was shown to be associated with autoimmunity and chronic inflammation [42]–[48], further illustrating that A20 is an important brake on the inflammatory response. The relevance of these findings for human disease has recently been illustrated through the identification of polymorphisms in the A20 locus that are associated with several autoimmune diseases and chronic inflammation [45]. In contrast to its well established function in the regulation of proinflammatory responses, the role of A20 in the regulation of antiviral immune responses is less well described and limited to a number of in vitro studies using overexpression or silencing in specific cell lines, indicating that A20 may regulate RIG-I- and TLR3-induced signaling to NF-κB and IRF-3 [49]–[52]. However, the precise in vivo role of A20 in the response to viral infection remains to be clarified. Using myeloid cell specific A20 knockout mice (A20myel-KO) that were recently generated in our lab and primary cells derived of these mice, we here provide evidence that A20 is a crucial negative regulator of IAV-induced proinflammatory and antiviral signaling in macrophages. Interestingly, A20myel-KO mice show enhanced survival and reduced morbidity in response to IAV lung infection compared to wild type mice. Protection against IAV in A20myel-KO mice is associated with increased cytokine and chemokine production, augmented recruitment of innate immune cells such as neutophils and alveolar macrophages, and enhanced viral clearance. These results suggest that boosting the innate immune response to IAV by targeting A20 activity in myeloid cells might have therapeutic potential."}

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PMC:3291650 / 7120-9432 JSON TXT