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  1 / 4426 MEDLINE  
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[PMID]:28747424
[Au] Autor:Schwartz C; Khan AR; Floudas A; Saunders SP; Hams E; Rodewald HR; McKenzie ANJ; Fallon PG
[Ad] Endereço:Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland.
[Ti] Título:ILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control.
[So] Source:J Exp Med;214(9):2507-2521, 2017 Sep 04.
[Is] ISSN:1540-9538
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Group 2 innate lymphoid cells (ILC2s) are important effector cells driving the initiation of type 2 immune responses leading to adaptive T helper 2 (Th2) immunity. Here we show that ILC2s dynamically express the checkpoint inhibitor molecule PD-L1 during type 2 pulmonary responses. Surprisingly, PD-L1:PD-1 interaction between ILC2s and CD4 T cells did not inhibit the T cell response, but PD-L1-expressing ILC2s stimulated increased expression of GATA3 and production of IL-13 by Th2 cells both in vitro and in vivo. Conditional deletion of PD-L1 on ILC2s impaired early Th2 polarization and cytokine production, leading to delayed worm expulsion during infection with the gastrointestinal helminth Our results identify a novel PD-L1-controlled mechanism for type 2 polarization, with ILC2s mediating an innate checkpoint to control adaptive T helper responses, which has important implications for the treatment of type 2 inflammation.
[Mh] Termos MeSH primário: Antígeno B7-H1/fisiologia
Linfócitos/fisiologia
Células Th2/fisiologia
[Mh] Termos MeSH secundário: Imunidade Adaptativa/imunologia
Imunidade Adaptativa/fisiologia
Animais
Antígeno B7-H1/imunologia
Fator de Transcrição GATA3/fisiologia
Imunidade Celular/imunologia
Imunidade Celular/fisiologia
Interleucina-13/fisiologia
Linfócitos/imunologia
Camundongos
Camundongos Endogâmicos C57BL
Nippostrongylus/imunologia
Infecções por Strongylida/imunologia
Células Th2/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (B7-H1 Antigen); 0 (Cd274 protein, mouse); 0 (GATA3 Transcription Factor); 0 (Gata3 protein, mouse); 0 (Interleukin-13)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1084/jem.20170051


  2 / 4426 MEDLINE  
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[PMID]:28459437
[Au] Autor:Toussaint M; Jackson DJ; Swieboda D; Guedán A; Tsourouktsoglou TD; Ching YM; Radermecker C; Makrinioti H; Aniscenko J; Bartlett NW; Edwards MR; Solari R; Farnir F; Papayannopoulos V; Bureau F; Marichal T; Johnston SL
[Ad] Endereço:Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College London, London, UK.
[Ti] Título:Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation.
[So] Source:Nat Med;23(6):681-691, 2017 06.
[Is] ISSN:1546-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Respiratory viral infections represent the most common cause of allergic asthma exacerbations. Amplification of the type-2 immune response is strongly implicated in asthma exacerbation, but how virus infection boosts type-2 responses is poorly understood. We report a significant correlation between the release of host double-stranded DNA (dsDNA) following rhinovirus infection and the exacerbation of type-2 allergic inflammation in humans. In a mouse model of allergic airway hypersensitivity, we show that rhinovirus infection triggers dsDNA release associated with the formation of neutrophil extracellular traps (NETs), known as NETosis. We further demonstrate that inhibiting NETosis by blocking neutrophil elastase or by degrading NETs with DNase protects mice from type-2 immunopathology. Furthermore, the injection of mouse genomic DNA alone is sufficient to recapitulate many features of rhinovirus-induced type-2 immune responses and asthma pathology. Thus, NETosis and its associated extracellular dsDNA contribute to the pathogenesis and may represent potential therapeutic targets of rhinovirus-induced asthma exacerbations.
[Mh] Termos MeSH primário: Asma/imunologia
Citocinas/imunologia
DNA/imunologia
Armadilhas Extracelulares/imunologia
Infecções por Picornaviridae/imunologia
Hipersensibilidade Respiratória/imunologia
Infecções Respiratórias/imunologia
Células Th2/imunologia
[Mh] Termos MeSH secundário: Adulto
Animais
Estudos de Casos e Controles
Dermatophagoides farinae/imunologia
Modelos Animais de Doenças
Feminino
Seres Humanos
Interferon gama/imunologia
Interleucina-13/imunologia
Interleucina-4/imunologia
Interleucina-5/imunologia
Masculino
Camundongos
Meia-Idade
Rhinovirus
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Interleukin-13); 0 (Interleukin-5); 207137-56-2 (Interleukin-4); 82115-62-6 (Interferon-gamma); 9007-49-2 (DNA)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1038/nm.4332


  3 / 4426 MEDLINE  
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[PMID]:28455782
[Au] Autor:Tripp CS; Cuff C; Campbell AL; Hendrickson BA; Voss J; Melim T; Wu C; Cherniack AD; Kim K
[Ad] Endereço:AbbVie, Global Pharmaceutical R&D, Worcester, MA, USA.
[Ti] Título:RPC4046, A Novel Anti-interleukin-13 Antibody, Blocks IL-13 Binding to IL-13 α1 and α2 Receptors: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation First-in-Human Study.
[So] Source:Adv Ther;34(6):1364-1381, 2017 Jun.
[Is] ISSN:1865-8652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: A unique anti-interleukin (IL)-13 monoclonal antibody, RPC4046, was generated on the basis of differential IL-13 receptor (R) blockade as assessed in a murine asthma model; the safety, tolerability, pharmacokinetics, and pharmacodynamics of RPC4046 were evaluated in a first-in-human study. METHODS: Anti-IL-13 antibodies with varying receptor blocking specificity were evaluated in the ovalbumin-induced murine asthma model. A randomized, double-blind, placebo-controlled, dose-escalation first-in-human study (NCT00986037) was conducted with RPC4046 in healthy adults and patients with mild to moderate controlled asthma. RESULTS: In the ovalbumin model, blocking IL-13 binding to both IL-13Rs (IL-13Rα1 and IL-13Rα2) inhibited more asthma phenotypic features and more fully normalized the distinct IL-13 gene transcription associated with asthma compared with blocking IL-13Rα1 alone. In humans, RPC4046 exposure increased dose-dependently; pharmacokinetics were similar in healthy and asthmatic subjects, and blockade of both IL-13Rs uniquely affected IL-13 gene transcription. A minority of participants (28%) had antidrug antibodies, which were transient and appeared not to affect pharmacokinetics. Adverse event profiles were similar in healthy and asthmatic subjects, without dose-related or administration route differences, systemic infusion-related reactions, or asthma symptom worsening. Adverse events were mild to moderate, with none reported as probably related to RPC4046 or leading to discontinuations. Non-serious upper respiratory tract infections were more frequent with RPC4046 versus placebo. CONCLUSION: RPC4046 is a novel anti-IL-13 antibody that blocks IL-13 binding to both receptors and more fully blocks the asthma phenotype. These results support further investigation of RPC4046 for IL-13-related allergic/inflammatory diseases (e.g., asthma and eosinophilic esophagitis). FUNDING: AbbVie Inc. sponsored the studies and contributed to the design and conduct of the studies, data management, data analysis, interpretation of the data, and in the preparation and approval of the manuscript.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/farmacologia
Anticorpos Monoclonais/uso terapêutico
Asma/tratamento farmacológico
Interleucina-13/antagonistas & inibidores
[Mh] Termos MeSH secundário: Adolescente
Adulto
Animais
Anticorpos Monoclonais/administração & dosagem
Anticorpos Monoclonais/efeitos adversos
Relação Dose-Resposta a Droga
Método Duplo-Cego
Feminino
Seres Humanos
Interleucina-13/imunologia
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Meia-Idade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (ABT-308); 0 (Antibodies, Monoclonal); 0 (Interleukin-13)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:T
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1007/s12325-017-0525-8


  4 / 4426 MEDLINE  
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[PMID]:29334288
[Au] Autor:Ntontsi P; Papathanassiou E; Loukides S; Bakakos P; Hillas G
[Ad] Endereço:a 2nd Respiratory Medicine Department , National and Kapodistrian University of Athens, Medical School, Attikon Hospital , Athens , Greece.
[Ti] Título:Targeted anti-IL-13 therapies in asthma: current data and future perspectives.
[So] Source:Expert Opin Investig Drugs;27(2):179-186, 2018 Feb.
[Is] ISSN:1744-7658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The identification of patients with severe asthma who will benefit from a personalized management approach remains an unmet need. Interleukin-13 (IL-13) is a cytokine possessing a significant role in asthma pathogenesis and progression of disease. Humanised monoclonal antibodies against IL-13 and IL-13 and IL-4 receptors are mainly proposed as add-on therapy in patients with T 2-high inflammation with uncontrolled asthma despite maximum therapy. Areas covered: The role of IL-13 in airway inflammation in severe asthma, the targeted anti-IL-13 therapies and biomarkers that predict response to anti-IL-13 treatment are discussed. Expert opinion: New effective individualized therapies in severe asthma are urgently needed to block specific inflammatory pathways using monoclonal antibodies. Studies on anti-IL-13 therapies showed that asthmatic patients could benefit from this novel targeted therapy as far as lung function and exacerbation rate are concerned. T 2-high and especially periostin-high groups of asthmatics with moderate-to-severe uncontrolled asthma seem to compose the group that could benefit from anti-IL-13 therapy. Targeting IL-13 alone may not be sufficient to achieve asthma control. Inhibition of IL-13 and IL-4 with mabs may be more encouraging and patients will probably have additional benefits from these therapeutic interventions because of IL-13/IL-4 overlapping actions in asthma pathophysiology.
[Mh] Termos MeSH primário: Antiasmáticos/farmacologia
Asma/tratamento farmacológico
Interleucina-13/imunologia
[Mh] Termos MeSH secundário: Animais
Antiasmáticos/imunologia
Anticorpos Monoclonais Humanizados/imunologia
Anticorpos Monoclonais Humanizados/farmacologia
Asma/imunologia
Seres Humanos
Inflamação/tratamento farmacológico
Inflamação/imunologia
Terapia de Alvo Molecular
Medicina de Precisão/métodos
Receptores de Interleucina-13/imunologia
Receptores de Interleucina-4/imunologia
Índice de Gravidade de Doença
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Asthmatic Agents); 0 (Antibodies, Monoclonal, Humanized); 0 (Interleukin-13); 0 (Receptors, Interleukin-13); 0 (Receptors, Interleukin-4)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180116
[St] Status:MEDLINE
[do] DOI:10.1080/13543784.2018.1427729


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[PMID]:29381928
[Au] Autor:Liao N; Zhao H; Chen ML; Xie ZF
[Ad] Endereço:Department of Geriatrics and Gerontology, First Affiliated Hospital, Guangxi Medical University, Nanning, China.
[Ti] Título:Association of the IL-13 polymorphisms rs1800925 and rs20541 with chronic obstructive pulmonary disease risk: An updated meta-analysis.
[So] Source:Medicine (Baltimore);96(47):e8556, 2017 Nov.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to investigate if 2 common single nucleotide polymorphisms (SNPs) in the interleukin-13 (IL-13) gene, rs1800925 and rs20541 are associated with chronic obstructive pulmonary disease (COPD) risk.Case-control association studies were retrieved systematically from PubMed, Scopus, ISI Web of Science, China National Knowledge Infrastructure, and Wanfang databases using standardized subject terms.Eleven studies including 3077 participants (1896 cases and 1181 controls) were analyzed. Evidence for a positive association between the T allele of the IL-13 SNP rs1800925 and COPD risk was found in the overall population (odds ratio [OR] = 1.57, 95% confidence interval [95% CI]: 1.21-2.04, Pz = .001). In subgroup analysis according to ethnicity, the T allele of rs1800925 was associated with an increased risk of COPD in Asians (OR = 1.88, 95% CI: 1.23-2.87, Pz = .004) and Caucasians (OR = 1.30, 95% CI: 1.01-1.67, Pz = .041), respectively. For rs20541, the results suggested an association between rs20541 and COPD risk in Caucasians under the recessive model (OR = 2.79, 95% CI: 1.13-6.92, Pz = .026), whereas this SNP was not associated with COPD in Asians.This meta-analysis suggests that the T allele of rs1800925 is associated with the increased risk of COPD in both Asians and Caucasians, whereas rs20541 is associated with the risk of COPD in Caucasians but not in Asians.
[Mh] Termos MeSH primário: Interleucina-13/genética
Doença Pulmonar Obstrutiva Crônica/genética
[Mh] Termos MeSH secundário: Grupo com Ancestrais do Continente Asiático/genética
Estudos de Casos e Controles
China
Grupos Étnicos
Grupo com Ancestrais do Continente Europeu/genética
União Europeia
Predisposição Genética para Doença
Seres Humanos
Razão de Chances
Polimorfismo de Nucleotídeo Único
Doença Pulmonar Obstrutiva Crônica/etnologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (Interleukin-13)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008556


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[PMID]:29390465
[Au] Autor:Mei Q; Qu J
[Ad] Endereço:Department of Intensive Care Unit, The First People's Hospital of Changde City, Changde, Hunan.
[Ti] Título:Interleukin-13 +2044 G/A and +1923C/T polymorphisms are associated with asthma susceptibility in Asians: A meta-analysis.
[So] Source:Medicine (Baltimore);96(51):e9203, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A number of studies have reported that the interleukin 13 (IL-13) gene is associated with asthma susceptibility. However, the reported relationships between the +2044G/A and +1923C/T polymorphisms and asthma susceptibility are inconsistent, especially in Asian adults and children with atopic status. Meta-analysis was used to analyze combined data.The +2044G/A and +1923C/T polymorphisms were investigated using data from 18 and 11 studies, respectively. The results suggested that there was an association between asthma and the IL-13 +2044G/A polymorphisms: odds ratio (OR) 1.34, 95% confidence interval (CI) 1.03-1.75 for AA versus GG + GA and +1923C/T; OR 1.50, 95% CI 1.26-1.78 for TT versus CC; and OR 1.15, 95% CI 1.10-1.21 for TC versus CC. The subgroup meta-analysis demonstrated that IL-13 +2044G/A polymorphisms are associated with asthma: OR 1.47, 95% CI 1.06-2.04 for AA versus GG + GA and +1923C/T; OR 1.70, 95% CI 1.26-2.30 for TT versus CC; and OR 1.27, 95% CI 1.03-1.56 for TC versus CC. In particular, IL-13 +2044G/A polymorphisms are specifically associated with Asian ethnicity in both adults and children with atopic status. However, the 1923C/T polymorphisms were not significantly associated with age group or atopic status within the Asian subgroups. Further investigation using larger samples and meta-analysis is required. No publication bias was detected.This meta-analysis indicates that the IL13 +2044G/A and +1923C/T polymorphisms are risk factors for asthma, especially among Asians.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Asiático/genética
Asma/etnologia
Asma/genética
Predisposição Genética para Doença/etnologia
Interleucina-13/genética
[Mh] Termos MeSH secundário: Adulto
Criança
China/epidemiologia
Seres Humanos
Incidência
Polimorfismo Genético
Medição de Risco
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Interleukin-13)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009203


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[PMID]:29304038
[Au] Autor:Madhankumar AB; Mrowczynski OD; Slagle-Webb B; Ravi V; Bourcier AJ; Payne R; Harbaugh KS; Rizk E; Connor JR
[Ad] Endereço:Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, PA, United States of America.
[Ti] Título:Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors.
[So] Source:PLoS One;13(1):e0181529, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peripheral nerve sheath tumors are benign tumors that have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs). Interleukin-13 receptor alpha 2 (IL13Rα2) is a cancer associated receptor expressed in glioblastoma and other invasive cancers. We analyzed IL13Rα2 expression in several MPNST cell lines including the STS26T cell line, as well as in several peripheral nerve sheath tumors to utilize the IL13Rα2 receptor as a target for therapy. In our studies, we demonstrated the selective expression of IL13Rα2 in several peripheral nerve sheath tumors by immunohistochemistry (IHC) and immunoblots. We established a sciatic nerve MPNST mouse model in NIH III nude mice using a luciferase transfected STS26T MPNST cell line. Similarly, analysis of the mouse sciatic nerves after tumor induction revealed significant expression of IL13Rα2 by IHC when compared to a normal sciatic nerve. IL13 conjugated liposomal doxorubicin was formulated and shown to bind and internalized in the MPNST cell culture model demonstrating cytotoxic effect. Our subsequent in vivo investigation in the STS26T MPNST sciatic nerve tumor model indicated that IL13 conjugated liposomal doxorubicin (IL13LIPDXR) was more effective in inhibiting tumor progression compared to unconjugated liposomal doxorubicin (LIPDXR). This further supports that IL13 receptor targeted nanoliposomes is a potential approach for treating MPNSTs.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/administração & dosagem
Doxorrubicina/análogos & derivados
Neoplasias da Bainha Neural/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antibióticos Antineoplásicos/farmacocinética
Linhagem Celular Tumoral
Doxorrubicina/administração & dosagem
Doxorrubicina/farmacocinética
Sistemas de Liberação de Medicamentos
Seres Humanos
Imuno-Histoquímica
Interleucina-13/administração & dosagem
Subunidade alfa2 de Receptor de Interleucina-13/metabolismo
Antígeno Ki-67/metabolismo
Camundongos
Camundongos Nus
Neoplasias da Bainha Neural/imunologia
Neoplasias da Bainha Neural/metabolismo
Polietilenoglicóis/administração & dosagem
Polietilenoglicóis/farmacocinética
Proteínas S100/metabolismo
Neuropatia Ciática/tratamento farmacológico
Neuropatia Ciática/imunologia
Neuropatia Ciática/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Interleukin-13); 0 (Interleukin-13 Receptor alpha2 Subunit); 0 (Ki-67 Antigen); 0 (Mki67 protein, mouse); 0 (S100 Proteins); 0 (liposomal doxorubicin); 30IQX730WE (Polyethylene Glycols); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181529


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[PMID]:28455433
[Au] Autor:Nie Y; Sun L; Wu Y; Yang Y; Wang J; He H; Hu Y; Chang Y; Liang Q; Zhu J; Ye RD; Christman JW; Qian F
[Ad] Endereço:Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
[Ti] Título:AKT2 Regulates Pulmonary Inflammation and Fibrosis via Modulating Macrophage Activation.
[So] Source:J Immunol;198(11):4470-4480, 2017 06 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Idiopathic pulmonary fibrosis (IPF) is a highly lethal pathological process that is characterized by inflammation, fibroblast accumulation, and excessive collagen deposition. Although AKT2-mediated signaling pathways modulate inflammatory responses, their role in IPF has not been defined. We report that AKT2 deficiency ( ) protected against bleomycin-induced pulmonary fibrosis and inflammation. Adoptive transfer of wild-type macrophages or administration of IL-13 to mice could restore pulmonary fibrosis. In response to IL-33 treatment, macrophages displayed decreased production of IL-13 and TGF-ß1 and attenuated phosphorylation of FoxO3a compared with macrophages. Furthermore, the expression of IL-13 was increased by small interfering RNA knockdown of FoxO3a or in FoxO3a-deficient macrophages. By evaluating lung sections from pulmonary fibrosis patients, we found that the phosphorylation of AKT2 and FoxO3a was remarkably upregulated. Collectively, these results indicate that AKT2 modulates pulmonary fibrosis through inducing TGF-ß1 and IL-13 production by macrophages, and inhibition of AKT2 may be a potential strategy for treating IPF.
[Mh] Termos MeSH primário: Ativação de Macrófagos
Pneumonia/imunologia
Proteínas Proto-Oncogênicas c-akt/metabolismo
Fibrose Pulmonar/imunologia
[Mh] Termos MeSH secundário: Transferência Adotiva
Animais
Bleomicina/administração & dosagem
Bleomicina/efeitos adversos
Proteína Forkhead Box O3/genética
Proteína Forkhead Box O3/metabolismo
Regulação da Expressão Gênica
Seres Humanos
Interleucina-13/administração & dosagem
Interleucina-13/genética
Interleucina-13/imunologia
Interleucina-33/imunologia
Interleucina-33/farmacologia
Macrófagos/imunologia
Camundongos
Proteínas Proto-Oncogênicas c-akt/deficiência
Proteínas Proto-Oncogênicas c-akt/genética
Fator de Crescimento Transformador beta1/genética
Fator de Crescimento Transformador beta1/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (FOXO3 protein, human); 0 (Forkhead Box Protein O3); 0 (FoxO3 protein, mouse); 0 (Il33 protein, mouse); 0 (Interleukin-13); 0 (Interleukin-33); 0 (Transforming Growth Factor beta1); 11056-06-7 (Bleomycin); EC 2.7.11.1 (AKT2 protein, human); EC 2.7.11.1 (Akt2 protein, mouse); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180127
[Lr] Data última revisão:
180127
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601503


  9 / 4426 MEDLINE  
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[PMID]:28450970
[Au] Autor:Song J; Heijink IH; Kistemaker LEM; Reinders-Luinge M; Kooistra W; Noordhoek JA; Gosens R; Brandsma CA; Timens W; Hiemstra PS; Rots MG; Hylkema MN
[Ad] Endereço:Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
[Ti] Título:Aberrant DNA methylation and expression of SPDEF and FOXA2 in airway epithelium of patients with COPD.
[So] Source:Clin Epigenetics;9:42, 2017.
[Is] ISSN:1868-7083
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Goblet cell metaplasia, a common feature of chronic obstructive pulmonary disease (COPD), is associated with mucus hypersecretion which contributes to the morbidity and mortality among patients. Transcription factors SAM-pointed domain-containing Ets-like factor (SPDEF) and forkhead box protein A2 (FOXA2) regulate goblet cell differentiation. This study aimed to (1) investigate DNA methylation and expression of and during goblet cell differentiation and (2) compare this in airway epithelial cells from patients with COPD and controls during mucociliary differentiation. METHODS: To assess DNA methylation and expression of and during goblet cell differentiation, primary airway epithelial cells, isolated from trachea (non-COPD controls) and bronchial tissue (patients with COPD), were differentiated by culture at the air-liquid interface (ALI) in the presence of cytokine interleukin (IL)-13 to promote goblet cell differentiation. RESULTS: We found that expression was induced during goblet cell differentiation, while expression was decreased. Importantly, CpG number 8 in the promoter was hypermethylated upon differentiation, whereas DNA methylation of promoter was not changed. In the absence of IL-13, COPD-derived ALI-cultured cells displayed higher expression than control-derived ALI cultures, whereas no difference was found for expression. This was accompanied with hypomethylation of CpG number 6 in the promoter and also hypomethylation of CpG numbers 10 and 11 in the promoter. CONCLUSIONS: These findings suggest that aberrant DNA methylation of and is one of the factors underlying mucus hypersecretion in COPD, opening new avenues for epigenetic-based inhibition of mucus hypersecretion.
[Mh] Termos MeSH primário: Brônquios/citologia
Metilação de DNA
Fator 3-beta Nuclear de Hepatócito/genética
Proteínas Proto-Oncogênicas c-ets/genética
Doença Pulmonar Obstrutiva Crônica/genética
Traqueia/citologia
[Mh] Termos MeSH secundário: Brônquios/efeitos dos fármacos
Diferenciação Celular
Células Cultivadas
Ilhas de CpG
Células Epiteliais/citologia
Feminino
Regulação da Expressão Gênica
Células Caliciformes/citologia
Seres Humanos
Interleucina-13/farmacologia
Masculino
Meia-Idade
Regiões Promotoras Genéticas
Traqueia/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (FOXA2 protein, human); 0 (Interleukin-13); 0 (Proto-Oncogene Proteins c-ets); 0 (SPDEF protein, human); 135845-92-0 (Hepatocyte Nuclear Factor 3-beta)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180122
[Lr] Data última revisão:
180122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1186/s13148-017-0341-7


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[PMID]:29199257
[Au] Autor:Yokota-Nakatsuma A
[Ad] Endereço:Laboratory of Immunology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University.
[Ti] Título:[Retinoic Acid Prevents Dendritic Cells from Inducing Novel Inflammatory T Cells That Produce Abundant Interleukin-13].
[So] Source:Yakugaku Zasshi;137(12):1491-1496, 2017.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:Vitamin A (VA) plays critical roles in gut homeostasis. Dendritic cells in mesenteric lymph nodes (MLN-DCs) can metabolize VA to retinoic acid (RA), thereby inducing gut-tropic lymphocytes and enhancing peripheral differentiation of regulatory T cells expressing forkhead box P3. We found that MLN-DCs from VA-deficient mice induced a distinct inflammatory T helper type 2 (Th2)-cell subset that produced abundant interleukin-13 (IL-13) and expressed receptors for homing to skin and inflammatory sites but not to the intestine. IL-6-neutralizing antibodies or RA abrogated the induction of this subset. On the other hand, RA receptor antagonists allowed MLN-DCs from VA-sufficient mice to induce a similar T-cell subset. IL-6 induced the differentiation of this subset from naive CD4 T cells upon activation with antibodies against CD3 and CD28, and RA receptor antagonists enhanced this induction. It has been considered that VA deficiency reduces Th2-dependent antibody responses. However, oral administration of an antigen to VA-deficient mice failed to induce immune tolerance but primed strong IL-13-dependent immunoglobulin G1 (IgG1) responses and IgE responses that caused skin allergy. These results suggest that MLN-DCs possess the latent ability to induce IL-13-producing inflammatory Th2 cells and that RA prevents them from inducing IL-13-dependent allergic or inflammatory responses to orally administered antigens.
[Mh] Termos MeSH primário: Células Dendríticas/imunologia
Interleucina-13/biossíntese
Células Th2/imunologia
Tretinoína/farmacologia
[Mh] Termos MeSH secundário: Animais
Linfócitos T CD4-Positivos/imunologia
Hipersensibilidade/imunologia
Imunoglobulina E/imunologia
Imunoglobulina G/imunologia
Inflamação/imunologia
Interleucina-13/imunologia
Interleucina-6
Linfonodos/citologia
Mesentério
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Immunoglobulin G); 0 (Interleukin-13); 0 (Interleukin-6); 37341-29-0 (Immunoglobulin E); 5688UTC01R (Tretinoin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.1248/yakushi.17-00153



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