PMC:3279418 / 1758-4724 JSON TXT

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2_test

pmc-enju-pas

bionlp-st-ge-2016-coref

{"project":"bionlp-st-ge-2016-coref","denotations":[{"id":"T1959","span":{"begin":127,"end":139},"obj":"Anaphor"},{"id":"T1960","span":{"begin":13,"end":20},"obj":"Antecedent"},{"id":"T1961","span":{"begin":432,"end":436},"obj":"Anaphor"},{"id":"T1962","span":{"begin":239,"end":246},"obj":"Antecedent"},{"id":"T1963","span":{"begin":462,"end":490},"obj":"Anaphor"}],"relations":[{"id":"R1725","pred":"boundBy","subj":"T1963","obj":"T1962"},{"id":"R1723","pred":"boundBy","subj":"T1959","obj":"T1960"},{"id":"R1724","pred":"boundBy","subj":"T1961","obj":"T1962"}],"namespaces":[{"prefix":"_base","uri":"https://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"Introduction\nSHARPIN was originally identified in post-synaptic densities of excitatory synapses in the brain of rats [1], but this protein is widely expressed in a variety of tissues [2]. Two allelic, autosomal recessive mutations in the Sharpin gene occurred spontaneously in two inbred strains of mice, C57B/KaLawRij-Sharpincpdm/Sharpincpdm and CBy.Ocb3/Dem-Sharpincpdm-Dem/Sharpincpdm-Dem, resulting in premature termination of mRNA synthesis and absence of a functional protein product [2]. Despite different genetic backgrounds, both mutations cause similar inflammatory disease with severe chronic progressive dermatitis and defective development of secondary lymphoid organs [2]–[4]. The dermatitis becomes clinically apparent at about four weeks of age. There are accumulations of eosinophils, neutrophils and macrophages in the skin of Sharpincpdm/Sharpincpdm mutant mice (hereafter referred to as cpdm mice) associated with increased expression of Th2 cytokines in the skin and in the supernatants of activated splenocytes [5]. The mice have an impaired delayed type hypersensitivity response and decreased secretion of IFNγ [5], indicating a defect in Th1 immune responses and a bias towards a Th2 immune response. Systemic treatment of cpdm mice with recombinant IL12 caused complete remission of the dermatitis [5]. Neutralization of IL5 by antibody treatment or crosses with IL5-deficient mice reduced the number of circulating and cutaneous eosinophils, but failed to reduce the onset and severity of the dermatitis [6].\nRecently, three independent groups identified SHARPIN as an essential component of the linear ubiquitin chain assembly complex (LUBAC) that regulates TNFα-induced canonical NF-κB signaling [7]–[9]. SHARPIN-deficient mouse embryonic fibroblast (MEF) were sensitized to TNFα-induced apoptosis and cell death was implicated as a factor in the dermatitis of cpdm mice [7]–[9].\nDendritic cells (DC) have a sentinel role in sensing pathogen or danger signals and initiate and direct activation of the adaptive immune response [10]. Activated and mature DC can carry processed antigenic peptides, migrate to lymphoid organs, and induce T-cell-mediated immune responses or tolerance. DC direct the differentiation of CD4+ T cells, and hence the type of immune response, through the selective secretion of cytokines. We hypothesized that defective cytokine secretion by DC contributed to the Th2-biased inflammatory phenotype in SHARPIN-deficient mice. The studies reported here found that lack of SHARPIN protein in BMDC caused defective expression of pro-inflammatory mediators and impaired NF-κB activation upon ligand stimulation. The ability of cpdm BMDC to stimulate Th1 cytokine production in allogeneic CD4+ T cells was compromised. Taken together, these results reveal that SHARPIN is a novel regulatory molecule in DC biology and suggest that the dysregulated function of SHARPIN-deficient DC plays a role in the cpdm phenotype."}

bionlp-st-ge-2016-spacy-parsed

UBERON-AE

{"project":"UBERON-AE","denotations":[{"id":"T946","span":{"begin":104,"end":109},"obj":"http://purl.obolibrary.org/obo/UBERON_0000955"},{"id":"T947","span":{"begin":176,"end":183},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"T948","span":{"begin":676,"end":682},"obj":"http://purl.obolibrary.org/obo/UBERON_0000062"},{"id":"T949","span":{"begin":2147,"end":2153},"obj":"http://purl.obolibrary.org/obo/UBERON_0000062"}],"text":"Introduction\nSHARPIN was originally identified in post-synaptic densities of excitatory synapses in the brain of rats [1], but this protein is widely expressed in a variety of tissues [2]. Two allelic, autosomal recessive mutations in the Sharpin gene occurred spontaneously in two inbred strains of mice, C57B/KaLawRij-Sharpincpdm/Sharpincpdm and CBy.Ocb3/Dem-Sharpincpdm-Dem/Sharpincpdm-Dem, resulting in premature termination of mRNA synthesis and absence of a functional protein product [2]. Despite different genetic backgrounds, both mutations cause similar inflammatory disease with severe chronic progressive dermatitis and defective development of secondary lymphoid organs [2]–[4]. The dermatitis becomes clinically apparent at about four weeks of age. There are accumulations of eosinophils, neutrophils and macrophages in the skin of Sharpincpdm/Sharpincpdm mutant mice (hereafter referred to as cpdm mice) associated with increased expression of Th2 cytokines in the skin and in the supernatants of activated splenocytes [5]. The mice have an impaired delayed type hypersensitivity response and decreased secretion of IFNγ [5], indicating a defect in Th1 immune responses and a bias towards a Th2 immune response. Systemic treatment of cpdm mice with recombinant IL12 caused complete remission of the dermatitis [5]. Neutralization of IL5 by antibody treatment or crosses with IL5-deficient mice reduced the number of circulating and cutaneous eosinophils, but failed to reduce the onset and severity of the dermatitis [6].\nRecently, three independent groups identified SHARPIN as an essential component of the linear ubiquitin chain assembly complex (LUBAC) that regulates TNFα-induced canonical NF-κB signaling [7]–[9]. SHARPIN-deficient mouse embryonic fibroblast (MEF) were sensitized to TNFα-induced apoptosis and cell death was implicated as a factor in the dermatitis of cpdm mice [7]–[9].\nDendritic cells (DC) have a sentinel role in sensing pathogen or danger signals and initiate and direct activation of the adaptive immune response [10]. Activated and mature DC can carry processed antigenic peptides, migrate to lymphoid organs, and induce T-cell-mediated immune responses or tolerance. DC direct the differentiation of CD4+ T cells, and hence the type of immune response, through the selective secretion of cytokines. We hypothesized that defective cytokine secretion by DC contributed to the Th2-biased inflammatory phenotype in SHARPIN-deficient mice. The studies reported here found that lack of SHARPIN protein in BMDC caused defective expression of pro-inflammatory mediators and impaired NF-κB activation upon ligand stimulation. The ability of cpdm BMDC to stimulate Th1 cytokine production in allogeneic CD4+ T cells was compromised. Taken together, these results reveal that SHARPIN is a novel regulatory molecule in DC biology and suggest that the dysregulated function of SHARPIN-deficient DC plays a role in the cpdm phenotype."}

GO-BP

GO-MF

{"project":"GO-MF","denotations":[{"id":"T2038","span":{"begin":1355,"end":1363},"obj":"http://purl.obolibrary.org/obo/GO_0003823"},{"id":"T2039","span":{"begin":1631,"end":1640},"obj":"http://purl.obolibrary.org/obo/GO_0031386"},{"id":"T2040","span":{"begin":2643,"end":2649},"obj":"http://purl.obolibrary.org/obo/GO_0005488"}],"text":"Introduction\nSHARPIN was originally identified in post-synaptic densities of excitatory synapses in the brain of rats [1], but this protein is widely expressed in a variety of tissues [2]. Two allelic, autosomal recessive mutations in the Sharpin gene occurred spontaneously in two inbred strains of mice, C57B/KaLawRij-Sharpincpdm/Sharpincpdm and CBy.Ocb3/Dem-Sharpincpdm-Dem/Sharpincpdm-Dem, resulting in premature termination of mRNA synthesis and absence of a functional protein product [2]. Despite different genetic backgrounds, both mutations cause similar inflammatory disease with severe chronic progressive dermatitis and defective development of secondary lymphoid organs [2]–[4]. The dermatitis becomes clinically apparent at about four weeks of age. There are accumulations of eosinophils, neutrophils and macrophages in the skin of Sharpincpdm/Sharpincpdm mutant mice (hereafter referred to as cpdm mice) associated with increased expression of Th2 cytokines in the skin and in the supernatants of activated splenocytes [5]. The mice have an impaired delayed type hypersensitivity response and decreased secretion of IFNγ [5], indicating a defect in Th1 immune responses and a bias towards a Th2 immune response. Systemic treatment of cpdm mice with recombinant IL12 caused complete remission of the dermatitis [5]. Neutralization of IL5 by antibody treatment or crosses with IL5-deficient mice reduced the number of circulating and cutaneous eosinophils, but failed to reduce the onset and severity of the dermatitis [6].\nRecently, three independent groups identified SHARPIN as an essential component of the linear ubiquitin chain assembly complex (LUBAC) that regulates TNFα-induced canonical NF-κB signaling [7]–[9]. SHARPIN-deficient mouse embryonic fibroblast (MEF) were sensitized to TNFα-induced apoptosis and cell death was implicated as a factor in the dermatitis of cpdm mice [7]–[9].\nDendritic cells (DC) have a sentinel role in sensing pathogen or danger signals and initiate and direct activation of the adaptive immune response [10]. Activated and mature DC can carry processed antigenic peptides, migrate to lymphoid organs, and induce T-cell-mediated immune responses or tolerance. DC direct the differentiation of CD4+ T cells, and hence the type of immune response, through the selective secretion of cytokines. We hypothesized that defective cytokine secretion by DC contributed to the Th2-biased inflammatory phenotype in SHARPIN-deficient mice. The studies reported here found that lack of SHARPIN protein in BMDC caused defective expression of pro-inflammatory mediators and impaired NF-κB activation upon ligand stimulation. The ability of cpdm BMDC to stimulate Th1 cytokine production in allogeneic CD4+ T cells was compromised. Taken together, these results reveal that SHARPIN is a novel regulatory molecule in DC biology and suggest that the dysregulated function of SHARPIN-deficient DC plays a role in the cpdm phenotype."}

GO-CC

{"project":"GO-CC","denotations":[{"id":"T2041","span":{"begin":50,"end":73},"obj":"http://purl.obolibrary.org/obo/GO_0014069"},{"id":"T2042","span":{"begin":77,"end":96},"obj":"http://purl.obolibrary.org/obo/GO_0060076"},{"id":"T2043","span":{"begin":88,"end":96},"obj":"http://purl.obolibrary.org/obo/GO_0045202"},{"id":"T2044","span":{"begin":1355,"end":1363},"obj":"http://purl.obolibrary.org/obo/GO_0019815"},{"id":"T2045","span":{"begin":1355,"end":1363},"obj":"http://purl.obolibrary.org/obo/GO_0042571"},{"id":"T2046","span":{"begin":1656,"end":1670},"obj":"http://purl.obolibrary.org/obo/GO_0071797"},{"id":"T2047","span":{"begin":1832,"end":1836},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T2048","span":{"begin":2168,"end":2172},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T2049","span":{"begin":2253,"end":2258},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T2050","span":{"begin":2746,"end":2751},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"Introduction\nSHARPIN was originally identified in post-synaptic densities of excitatory synapses in the brain of rats [1], but this protein is widely expressed in a variety of tissues [2]. Two allelic, autosomal recessive mutations in the Sharpin gene occurred spontaneously in two inbred strains of mice, C57B/KaLawRij-Sharpincpdm/Sharpincpdm and CBy.Ocb3/Dem-Sharpincpdm-Dem/Sharpincpdm-Dem, resulting in premature termination of mRNA synthesis and absence of a functional protein product [2]. Despite different genetic backgrounds, both mutations cause similar inflammatory disease with severe chronic progressive dermatitis and defective development of secondary lymphoid organs [2]–[4]. The dermatitis becomes clinically apparent at about four weeks of age. There are accumulations of eosinophils, neutrophils and macrophages in the skin of Sharpincpdm/Sharpincpdm mutant mice (hereafter referred to as cpdm mice) associated with increased expression of Th2 cytokines in the skin and in the supernatants of activated splenocytes [5]. The mice have an impaired delayed type hypersensitivity response and decreased secretion of IFNγ [5], indicating a defect in Th1 immune responses and a bias towards a Th2 immune response. Systemic treatment of cpdm mice with recombinant IL12 caused complete remission of the dermatitis [5]. Neutralization of IL5 by antibody treatment or crosses with IL5-deficient mice reduced the number of circulating and cutaneous eosinophils, but failed to reduce the onset and severity of the dermatitis [6].\nRecently, three independent groups identified SHARPIN as an essential component of the linear ubiquitin chain assembly complex (LUBAC) that regulates TNFα-induced canonical NF-κB signaling [7]–[9]. SHARPIN-deficient mouse embryonic fibroblast (MEF) were sensitized to TNFα-induced apoptosis and cell death was implicated as a factor in the dermatitis of cpdm mice [7]–[9].\nDendritic cells (DC) have a sentinel role in sensing pathogen or danger signals and initiate and direct activation of the adaptive immune response [10]. Activated and mature DC can carry processed antigenic peptides, migrate to lymphoid organs, and induce T-cell-mediated immune responses or tolerance. DC direct the differentiation of CD4+ T cells, and hence the type of immune response, through the selective secretion of cytokines. We hypothesized that defective cytokine secretion by DC contributed to the Th2-biased inflammatory phenotype in SHARPIN-deficient mice. The studies reported here found that lack of SHARPIN protein in BMDC caused defective expression of pro-inflammatory mediators and impaired NF-κB activation upon ligand stimulation. The ability of cpdm BMDC to stimulate Th1 cytokine production in allogeneic CD4+ T cells was compromised. Taken together, these results reveal that SHARPIN is a novel regulatory molecule in DC biology and suggest that the dysregulated function of SHARPIN-deficient DC plays a role in the cpdm phenotype."}

sentences

ICD10

{"project":"ICD10","denotations":[{"id":"T2033","span":{"begin":617,"end":627},"obj":"http://purl.bioontology.org/ontology/ICD10/L30.9"},{"id":"T2034","span":{"begin":696,"end":706},"obj":"http://purl.bioontology.org/ontology/ICD10/L30.9"},{"id":"T2035","span":{"begin":1314,"end":1324},"obj":"http://purl.bioontology.org/ontology/ICD10/L30.9"},{"id":"T2036","span":{"begin":1521,"end":1531},"obj":"http://purl.bioontology.org/ontology/ICD10/L30.9"},{"id":"T2037","span":{"begin":1877,"end":1887},"obj":"http://purl.bioontology.org/ontology/ICD10/L30.9"}],"text":"Introduction\nSHARPIN was originally identified in post-synaptic densities of excitatory synapses in the brain of rats [1], but this protein is widely expressed in a variety of tissues [2]. Two allelic, autosomal recessive mutations in the Sharpin gene occurred spontaneously in two inbred strains of mice, C57B/KaLawRij-Sharpincpdm/Sharpincpdm and CBy.Ocb3/Dem-Sharpincpdm-Dem/Sharpincpdm-Dem, resulting in premature termination of mRNA synthesis and absence of a functional protein product [2]. Despite different genetic backgrounds, both mutations cause similar inflammatory disease with severe chronic progressive dermatitis and defective development of secondary lymphoid organs [2]–[4]. The dermatitis becomes clinically apparent at about four weeks of age. There are accumulations of eosinophils, neutrophils and macrophages in the skin of Sharpincpdm/Sharpincpdm mutant mice (hereafter referred to as cpdm mice) associated with increased expression of Th2 cytokines in the skin and in the supernatants of activated splenocytes [5]. The mice have an impaired delayed type hypersensitivity response and decreased secretion of IFNγ [5], indicating a defect in Th1 immune responses and a bias towards a Th2 immune response. Systemic treatment of cpdm mice with recombinant IL12 caused complete remission of the dermatitis [5]. Neutralization of IL5 by antibody treatment or crosses with IL5-deficient mice reduced the number of circulating and cutaneous eosinophils, but failed to reduce the onset and severity of the dermatitis [6].\nRecently, three independent groups identified SHARPIN as an essential component of the linear ubiquitin chain assembly complex (LUBAC) that regulates TNFα-induced canonical NF-κB signaling [7]–[9]. SHARPIN-deficient mouse embryonic fibroblast (MEF) were sensitized to TNFα-induced apoptosis and cell death was implicated as a factor in the dermatitis of cpdm mice [7]–[9].\nDendritic cells (DC) have a sentinel role in sensing pathogen or danger signals and initiate and direct activation of the adaptive immune response [10]. Activated and mature DC can carry processed antigenic peptides, migrate to lymphoid organs, and induce T-cell-mediated immune responses or tolerance. DC direct the differentiation of CD4+ T cells, and hence the type of immune response, through the selective secretion of cytokines. We hypothesized that defective cytokine secretion by DC contributed to the Th2-biased inflammatory phenotype in SHARPIN-deficient mice. The studies reported here found that lack of SHARPIN protein in BMDC caused defective expression of pro-inflammatory mediators and impaired NF-κB activation upon ligand stimulation. The ability of cpdm BMDC to stimulate Th1 cytokine production in allogeneic CD4+ T cells was compromised. Taken together, these results reveal that SHARPIN is a novel regulatory molecule in DC biology and suggest that the dysregulated function of SHARPIN-deficient DC plays a role in the cpdm phenotype."}

events-check-again

bionlp-st-ge-2016-reference-tees

bionlp-st-ge-2016-reference

bionlp-st-ge-2016-uniprot

{"project":"bionlp-st-ge-2016-uniprot","denotations":[{"id":"T1964","span":{"begin":13,"end":20},"obj":"Q9H0F6"},{"id":"T1965","span":{"begin":239,"end":246},"obj":"Q9H0F6"},{"id":"T1966","span":{"begin":1348,"end":1351},"obj":"P05113"},{"id":"T1967","span":{"begin":1390,"end":1393},"obj":"P05113"},{"id":"T1968","span":{"begin":1583,"end":1590},"obj":"Q9H0F6"},{"id":"T1969","span":{"begin":1735,"end":1742},"obj":"Q9H0F6"},{"id":"T1970","span":{"begin":2246,"end":2249},"obj":"P01730"},{"id":"T1971","span":{"begin":2457,"end":2464},"obj":"Q9H0F6"},{"id":"T1972","span":{"begin":2526,"end":2533},"obj":"Q9H0F6"},{"id":"T1973","span":{"begin":2739,"end":2742},"obj":"P01730"},{"id":"T1974","span":{"begin":2811,"end":2818},"obj":"Q9H0F6"},{"id":"T1975","span":{"begin":2910,"end":2917},"obj":"Q9H0F6"}],"namespaces":[{"prefix":"_base","uri":"http://www.uniprot.org/uniprot/"}],"text":"Introduction\nSHARPIN was originally identified in post-synaptic densities of excitatory synapses in the brain of rats [1], but this protein is widely expressed in a variety of tissues [2]. Two allelic, autosomal recessive mutations in the Sharpin gene occurred spontaneously in two inbred strains of mice, C57B/KaLawRij-Sharpincpdm/Sharpincpdm and CBy.Ocb3/Dem-Sharpincpdm-Dem/Sharpincpdm-Dem, resulting in premature termination of mRNA synthesis and absence of a functional protein product [2]. Despite different genetic backgrounds, both mutations cause similar inflammatory disease with severe chronic progressive dermatitis and defective development of secondary lymphoid organs [2]–[4]. The dermatitis becomes clinically apparent at about four weeks of age. There are accumulations of eosinophils, neutrophils and macrophages in the skin of Sharpincpdm/Sharpincpdm mutant mice (hereafter referred to as cpdm mice) associated with increased expression of Th2 cytokines in the skin and in the supernatants of activated splenocytes [5]. The mice have an impaired delayed type hypersensitivity response and decreased secretion of IFNγ [5], indicating a defect in Th1 immune responses and a bias towards a Th2 immune response. Systemic treatment of cpdm mice with recombinant IL12 caused complete remission of the dermatitis [5]. Neutralization of IL5 by antibody treatment or crosses with IL5-deficient mice reduced the number of circulating and cutaneous eosinophils, but failed to reduce the onset and severity of the dermatitis [6].\nRecently, three independent groups identified SHARPIN as an essential component of the linear ubiquitin chain assembly complex (LUBAC) that regulates TNFα-induced canonical NF-κB signaling [7]–[9]. SHARPIN-deficient mouse embryonic fibroblast (MEF) were sensitized to TNFα-induced apoptosis and cell death was implicated as a factor in the dermatitis of cpdm mice [7]–[9].\nDendritic cells (DC) have a sentinel role in sensing pathogen or danger signals and initiate and direct activation of the adaptive immune response [10]. Activated and mature DC can carry processed antigenic peptides, migrate to lymphoid organs, and induce T-cell-mediated immune responses or tolerance. DC direct the differentiation of CD4+ T cells, and hence the type of immune response, through the selective secretion of cytokines. We hypothesized that defective cytokine secretion by DC contributed to the Th2-biased inflammatory phenotype in SHARPIN-deficient mice. The studies reported here found that lack of SHARPIN protein in BMDC caused defective expression of pro-inflammatory mediators and impaired NF-κB activation upon ligand stimulation. The ability of cpdm BMDC to stimulate Th1 cytokine production in allogeneic CD4+ T cells was compromised. Taken together, these results reveal that SHARPIN is a novel regulatory molecule in DC biology and suggest that the dysregulated function of SHARPIN-deficient DC plays a role in the cpdm phenotype."}

test2

PMC:3279418 / 1758-4724 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:3279418 / 1758-4724 JSON TXT