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  1 / 1336 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


  2 / 1336 MEDLINE  
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[PMID]:28694386
[Au] Autor:White AJ; Baik S; Parnell SM; Holland AM; Brombacher F; Jenkinson WE; Anderson G
[Ad] Endereço:Institute for Immunology and Immunotherapy, College of Medical and Dental Sciences, Medical School, University of Birmingham, Birmingham, England, UK.
[Ti] Título:A type 2 cytokine axis for thymus emigration.
[So] Source:J Exp Med;214(8):2205-2216, 2017 Aug 07.
[Is] ISSN:1540-9538
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the thymus, stromal microenvironments support a developmental program that generates mature T cells ready for thymic exit. The cellular and molecular specialization within thymic stromal cells that enables their regulation of specific stages of thymocyte development is poorly understood. Here, we show the thymic microenvironment expresses the type 2 IL-4R complex and is functionally responsive to its known ligands, IL-4 and IL-13. Absence of IL-4Rα limits thymocyte emigration, leading to an intrathymic accumulation of mature thymocytes within medullary perivascular spaces and reduced numbers of recent thymic emigrants. Thymus transplantation shows this requirement maps to IL-4Rα expression by stromal cells, and we provide evidence that it regulates thymic exit via a process distinct from S1P-mediated migration. Finally, we reveal a cellular mechanism by which IL-4 IL-13 invariant NKT cells are necessary for IL-4Rα signaling that regulates thymic exit. Collectively, we define a new axis for thymic emigration involving stimulation of the thymic microenvironment via type 2 cytokines from innate T cells.
[Mh] Termos MeSH primário: Receptores de Interleucina-4/fisiologia
Timo/fisiologia
[Mh] Termos MeSH secundário: Animais
Movimento Celular/fisiologia
Interleucina-13/fisiologia
Interleucina-4/fisiologia
Camundongos
Camundongos Knockout
Células T Matadoras Naturais/fisiologia
Transdução de Sinais/fisiologia
Timócitos/fisiologia
Timo/transplante
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukin-13); 0 (Receptors, Interleukin-4); 207137-56-2 (Interleukin-4)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170712
[St] Status:MEDLINE
[do] DOI:10.1084/jem.20170271


  3 / 1336 MEDLINE  
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[PMID]:28687632
[Au] Autor:Guo X; Li T; Xu Y; Xu X; Zhu Z; Zhang Y; Xu J; Xu K; Cheng H; Zhang X; Ke Y
[Ad] Endereço:From the Department of Pathology and Pathophysiology and Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
[Ti] Título:Increased levels of Gab1 and Gab2 adaptor proteins skew interleukin-4 (IL-4) signaling toward M2 macrophage-driven pulmonary fibrosis in mice.
[So] Source:J Biol Chem;292(34):14003-14015, 2017 Aug 25.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:M2-polarized macrophages, also known as alternatively activated macrophages, have long been associated with pulmonary fibrosis; however, the mechanism has not been fully defined. Gab1 and Gab2 proteins belong to the Gab family of adaptors and are integral components of the signal specificity in response to various extracellular stimuli. In this report, we found that levels of both Gab1 and Gab2 were elevated in M2-polarized macrophages isolated from bleomycin-induced fibrotic lungs. Gab1/2 deficiency in bone marrow-derived macrophages abrogated IL-4-mediated M2 polarization. Furthermore, conditional removal of (Gab1 ) and germ line knock-out of (Gab2 ) in macrophages prevented a bias toward the M2 phenotype and attenuated bleomycin-induced fibrotic lung remodeling. In support of these observations, Gab1/2 were involved in responses predominated by IL-4 signaling, an essential determinant for macrophage M2 polarization. Further investigation revealed that both Gab1 and -2 are recruited to the IL-4 receptor, synergistically enhancing downstream signal amplification but conferring IL-4 signal preference. Mechanistically, the loss of Gab1 attenuated AKT activation, whereas the absence of Gab2 suppressed STAT6 activation in response to IL-4 stimulation, both of which are commonly attributed to M2-driven pulmonary fibrosis in mice. Taken together, these observations define a non-redundant role of Gab docking proteins in M2 polarization, adding critical insights into the pathogenesis of idiopathic pulmonary fibrosis.
[Mh] Termos MeSH primário: Interleucina-4/metabolismo
Macrófagos/metabolismo
Fosfoproteínas/metabolismo
Fibrose Pulmonar/metabolismo
Receptores de Interleucina-4/agonistas
Transdução de Sinais
[Mh] Termos MeSH secundário: Remodelação das Vias Aéreas/efeitos dos fármacos
Animais
Bleomicina/toxicidade
Células da Medula Óssea/efeitos dos fármacos
Células da Medula Óssea/imunologia
Células da Medula Óssea/metabolismo
Células da Medula Óssea/patologia
Polaridade Celular/efeitos dos fármacos
Células Cultivadas
Cruzamentos Genéticos
Interleucina-4/genética
Pulmão/efeitos dos fármacos
Pulmão/imunologia
Pulmão/metabolismo
Pulmão/patologia
Ativação de Macrófagos/efeitos dos fármacos
Macrófagos/efeitos dos fármacos
Macrófagos/imunologia
Macrófagos/patologia
Camundongos Knockout
Camundongos Transgênicos
Fosfoproteínas/genética
Transporte Proteico/efeitos dos fármacos
Fibrose Pulmonar/induzido quimicamente
Fibrose Pulmonar/imunologia
Fibrose Pulmonar/patologia
Receptores de Interleucina-4/metabolismo
Proteínas Recombinantes/metabolismo
Mucosa Respiratória/efeitos dos fármacos
Mucosa Respiratória/imunologia
Mucosa Respiratória/metabolismo
Mucosa Respiratória/patologia
Transdução de Sinais/efeitos dos fármacos
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gab1 protein, mouse); 0 (Gab2 protein, mouse); 0 (Phosphoproteins); 0 (Receptors, Interleukin-4); 0 (Recombinant Proteins); 11056-06-7 (Bleomycin); 207137-56-2 (Interleukin-4)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170709
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.802066


  4 / 1336 MEDLINE  
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[PMID]:28507062
[Au] Autor:Pelly VS; Coomes SM; Kannan Y; Gialitakis M; Entwistle LJ; Perez-Lloret J; Czieso S; Okoye IS; Rückerl D; Allen JE; Brombacher F; Wilson MS
[Ad] Endereço:Allergy and Anti-Helminth Immunity Laboratory, Mill Hill Laboratory, The Francis Crick Institute, London NW7 1AA, England, UK.
[Ti] Título:Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths.
[So] Source:J Exp Med;214(6):1809-1826, 2017 Jun 05.
[Is] ISSN:1540-9538
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Immunity to intestinal helminth infections requires the rapid activation of T helper 2 cells (Th2 cells). However, simultaneous expansion of CD4 Foxp3 regulatory T cells (T reg cells) impedes protective responses, resulting in chronic infections. The ratio between T reg and effector T cells can therefore determine the outcome of infection. The redifferentiation of T reg cells into Th cells has been identified in hyperinflammatory diseases. In this study, we asked whether ex-T reg Th2 cells develop and contribute to type-2 immunity. Using multigene reporter and fate-reporter systems, we demonstrate that a significant proportion of Th2 cells derive from Foxp3 cells after infection and airway allergy. Ex-Foxp3 Th2 cells exhibit characteristic Th2 effector functions and provide immunity to Through selective deletion of on Foxp3 cells, we further demonstrate IL-4 is required for the development of ex-Foxp3 Th2 cells. Collectively, our findings indicate that converting T reg cells into Th2 cells could concomitantly enhance Th2 cells and limit T reg cell-mediated suppression.
[Mh] Termos MeSH primário: Fatores de Transcrição Forkhead/metabolismo
Imunidade
Interleucina-4/metabolismo
Intestinos/imunologia
Intestinos/parasitologia
Nematospiroides dubius/imunologia
Células Th2/imunologia
[Mh] Termos MeSH secundário: Transferência Adotiva
Animais
Polaridade Celular
Perfilação da Expressão Gênica
Imunidade/genética
Camundongos Endogâmicos C57BL
Receptores de Interleucina-4/metabolismo
Transdução de Sinais
Infecções por Strongylida/imunologia
Infecções por Strongylida/parasitologia
Linfócitos T Reguladores/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Forkhead Transcription Factors); 0 (Foxp3 protein, mouse); 0 (Receptors, Interleukin-4); 207137-56-2 (Interleukin-4)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170517
[St] Status:MEDLINE
[do] DOI:10.1084/jem.20161104


  5 / 1336 MEDLINE  
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[PMID]:28396317
[Au] Autor:Zilio S; Vella JL; De la Fuente AC; Daftarian PM; Weed DT; Kaifer A; Marigo I; Leone K; Bronte V; Serafini P
[Ad] Endereço:Department of Microbiology and Immunology, University of Miami, Miami, FL, 33136.
[Ti] Título:4PD Functionalized Dendrimers: A Flexible Tool for In Vivo Gene Silencing of Tumor-Educated Myeloid Cells.
[So] Source:J Immunol;198(10):4166-4177, 2017 May 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Myeloid cells play a key role in tumor progression and metastasis by providing nourishment and immune protection, as well as facilitating cancer invasion and seeding to distal sites. Although advances have been made in understanding the biology of these tumor-educated myeloid cells (TEMCs), their intrinsic plasticity challenges our further understanding of their biology. Indeed, in vitro experiments only mimic the in vivo setting, and current gene-knockout technologies do not allow the simultaneous, temporally controlled, and cell-specific silencing of multiple genes or pathways. In this article, we describe the 4PD nanoplatform, which allows the in vivo preferential transfection and in vivo tracking of TEMCs with the desired RNAs. This platform is based on the conjugation of CD124/IL-4Rα-targeting peptide with G5 PAMAM dendrimers as the loading surface and can convey therapeutic or experimental RNAs of interest. When injected i.v. in mice bearing CT26 colon carcinoma or B16 melanoma, the 4PD nanoparticles predominantly accumulate at the tumor site, transfecting intratumoral myeloid cells. The use of 4PD to deliver a combination of STAT3- and C/EBPß-specific short hairpin RNA or miR-142-3p confirmed the importance of these genes and microRNAs in TEMC biology and indicates that silencing of both genes is necessary to increase the efficacy of immune interventions. Thus, the 4PD nanoparticle can rapidly and cost effectively modulate and assess the in vivo function of microRNAs and mRNAs in TEMCs.
[Mh] Termos MeSH primário: Dendrímeros/metabolismo
Inativação Gênica
Células Mieloides/metabolismo
Nanotecnologia/métodos
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Neoplasias do Colo
Dendrímeros/administração & dosagem
Subunidade alfa de Receptor de Interleucina-4/imunologia
Subunidade alfa de Receptor de Interleucina-4/metabolismo
Melanoma Experimental
Camundongos
MicroRNAs
Células Mieloides/imunologia
Nanopartículas/administração & dosagem
Nanopartículas/metabolismo
Nanotecnologia/normas
Receptores de Interleucina-4/imunologia
Receptores de Interleucina-4/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dendrimers); 0 (Interleukin-4 Receptor alpha Subunit); 0 (MicroRNAs); 0 (PAMAM Starburst); 0 (Receptors, Interleukin-4)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170412
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1600833


  6 / 1336 MEDLINE  
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[PMID]:28165826
[Au] Autor:Kraft M; Worm M
[Ad] Endereço:a Department of Dermatology and Allergology , Allergy-Center-Charité, Charité - Universitätsmedizin Berlin , Berlin , Germany.
[Ti] Título:Dupilumab in the treatment of moderate-to-severe atopic dermatitis.
[So] Source:Expert Rev Clin Immunol;13(4):301-310, 2017 Apr.
[Is] ISSN:1744-8409
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Atopic dermatitis is a common inflammatory skin disease with an increasing prevalence. Treatment of patients suffering from mild or moderate disease includes the use of emollients and topical glucocorticoids or topical calcineurin inhibitors. Patients with chronic and severe atopic dermatitis where topical therapy is usually insufficient require the use of systemic immunosuppressive drugs, which is often limited due to toxicity and severe adverse effects. Areas covered: This review summarizes the literature on the mechanism of action, clinical efficacy and safety of dupilumab, a monoclonal antibody that targets the α-subunit of the interleukin-4 receptor (IL-4Rα) leading to the inhibition of both the IL-4 and IL-13 pathways. A literature search was performed on Pubmed and ClinicalTrials.gov using key words 'dupilumab', 'REGN668', 'IL-4'/'IL-13' and 'atopic dermatitis'. Expert commentary: Dupilumab offers an innovative therapeutic approach for moderate-to-severe atopic dermatitis. It is not approved for clinical use in any country yet; however, due to its excellent clinical efficacy and a favorable safety profile, dupilumab may revolutionize the treatment of moderate-to-severe atopic dermatitis in the next upcoming years.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/uso terapêutico
Dermatite Atópica/tratamento farmacológico
Imunossupressores/uso terapêutico
Interleucina-13/antagonistas & inibidores
Interleucina-4/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Terapia Biológica
Seres Humanos
Receptores de Interleucina-4/imunologia
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Immunosuppressive Agents); 0 (Interleukin-13); 0 (Receptors, Interleukin-4); 0 (SAR231893); 207137-56-2 (Interleukin-4)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170207
[St] Status:MEDLINE
[do] DOI:10.1080/1744666X.2017.1292134


  7 / 1336 MEDLINE  
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[PMID]:28142034
[Au] Autor:Cho YA; Kim J
[Ad] Endereço:Molecular Epidemiology Branch, National Cancer Center, Goyang, South Korea.
[Ti] Título:Association of IL4, IL13, and IL4R polymorphisms with gastrointestinal cancer risk: A meta-analysis.
[So] Source:J Epidemiol;27(5):215-220, 2017 May.
[Is] ISSN:1349-9092
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Previous studies have suggested that IL4, IL13, and IL4R are associated with serum IgE levels and allergies, and common variants of these genes may alter cancer risk. To clarify these associations, we conducted a meta-analysis to investigate the associations of IL4, IL13, and IL4R polymorphisms with gastrointestinal cancer risk. METHODS: We used 27 eligible case-control studies describing the associations of six polymorphisms of IL4, IL13, and IL4R with gastrointestinal cancer risk to calculate summary odds ratios (ORs) and 95% confidence intervals (CIs) using five different genetic models. The Q-statistic and I statistic were calculated to examine heterogeneity. RESULTS: The IL4 rs2070874 T allele seems to be associated with an increased risk of gastrointestinal cancer (OR 1.11; 95% CI, 1.00-1.24 for T allele vs. C allele). This association was significant in studies conducted outside of Asia (OR 1.28; 95% CI, 1.03-1.58 for T allele vs. C allele) and in studies investigating the association with gastric cancer (OR 1.17; 95% CI, 1.03-1.34 for T allele vs. C allele). However, the IL4R rs1801275 heterozygote seems to be associated with a reduced risk of gastrointestinal cancer (OR 0.79; 95% CI, 0.65-0.96 for AG vs. AA). Other polymorphisms did not show any significant associations with gastrointestinal cancer risk in any of the genetic models and subgroup analyses. CONCLUSIONS: Our results suggest that certain polymorphisms of IL4 and IL4R may affect susceptibility to gastrointestinal cancer. However, further studies are required to confirm these findings.
[Mh] Termos MeSH primário: Neoplasias Gastrointestinais/genética
Predisposição Genética para Doença
Interleucina-13/genética
Subunidade alfa de Receptor de Interleucina-4/genética
Interleucina-4/genética
Polimorfismo de Nucleotídeo Único/genética
Receptores de Interleucina-4/genética
[Mh] Termos MeSH secundário: Neoplasias Gastrointestinais/diagnóstico
Seres Humanos
Hipersensibilidade
Imunoglobulina E/sangue
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (IL4 protein, human); 0 (IL4R protein, human); 0 (Interleukin-13); 0 (Interleukin-4 Receptor alpha Subunit); 0 (Receptors, Interleukin-4); 207137-56-2 (Interleukin-4); 37341-29-0 (Immunoglobulin E)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170201
[St] Status:MEDLINE


  8 / 1336 MEDLINE  
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[PMID]:28126831
[Au] Autor:Lyons JJ; Liu Y; Ma CA; Yu X; O'Connell MP; Lawrence MG; Zhang Y; Karpe K; Zhao M; Siegel AM; Stone KD; Nelson C; Jones N; DiMaggio T; Darnell DN; Mendoza-Caamal E; Orozco L; Hughes JD; McElwee J; Hohman RJ; Frischmeyer-Guerrerio PA; Rothenberg ME; Freeman AF; Holland SM; Milner JD
[Ad] Endereço:Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
[Ti] Título:ERBIN deficiency links STAT3 and TGF-ß pathway defects with atopy in humans.
[So] Source:J Exp Med;214(3):669-680, 2017 Mar 06.
[Is] ISSN:1540-9538
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nonimmunological connective tissue phenotypes in humans are common among some congenital and acquired allergic diseases. Several of these congenital disorders have been associated with either increased TGF-ß activity or impaired STAT3 activation, suggesting that these pathways might intersect and that their disruption may contribute to atopy. In this study, we show that STAT3 negatively regulates TGF-ß signaling via ERBB2-interacting protein (ERBIN), a SMAD anchor for receptor activation and SMAD2/3 binding protein. Individuals with dominant-negative mutations ( ) or a loss-of-function mutation in ( ) have evidence of deregulated TGF-ß signaling with increased regulatory T cells and total FOXP3 expression. These naturally occurring mutations, recapitulated in vitro, impair STAT3-ERBIN-SMAD2/3 complex formation and fail to constrain nuclear pSMAD2/3 in response to TGF-ß. In turn, cell-intrinsic deregulation of TGF-ß signaling is associated with increased functional IL-4Rα expression on naive lymphocytes and can induce expression and activation of the IL-4/IL-4Rα/GATA3 axis in vitro. These findings link increased TGF-ß pathway activation in and patient lymphocytes with increased T helper type 2 cytokine expression and elevated IgE.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/fisiologia
Hipersensibilidade/imunologia
Fator de Transcrição STAT3/fisiologia
Transdução de Sinais/fisiologia
Fator de Crescimento Transformador beta/fisiologia
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/deficiência
Seres Humanos
Interleucina-4/fisiologia
Receptores de Interleucina-4/fisiologia
Proteína Smad2/análise
Proteína Smad2/fisiologia
Proteína Smad3/análise
Proteína Smad3/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (ERBB2IP protein, human); 0 (Receptors, Interleukin-4); 0 (SMAD2 protein, human); 0 (SMAD3 protein, human); 0 (STAT3 Transcription Factor); 0 (STAT3 protein, human); 0 (Smad2 Protein); 0 (Smad3 Protein); 0 (Transforming Growth Factor beta); 207137-56-2 (Interleukin-4)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170128
[St] Status:MEDLINE
[do] DOI:10.1084/jem.20161435


  9 / 1336 MEDLINE  
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[PMID]:28093225
[Au] Autor:Liu Y; Zhang H; Ni R; Jia WQ; Wang YY
[Ad] Endereço:Department of Respiration Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China. Electronic address: liuying03341237@126.com.
[Ti] Título:IL-4R suppresses airway inflammation in bronchial asthma by inhibiting the IL-4/STAT6 pathway.
[So] Source:Pulm Pharmacol Ther;43:32-38, 2017 Apr.
[Is] ISSN:1522-9629
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: This study aims to explore the mechanisms of how IL-4R suppresses airway inflammation in bronchial asthma by inhibiting the IL-4/STAT6 pathway. METHODS: A total of 27 BALB/c male mice were selected and divided into control, asthma and IL-4R groups. Ovalbumin-induced mouse asthma model was established. Maximal pulmonary resistance was recorded. Hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining were conducted to observe the pathological changes in lung tissue. Optical microscope was used to detect numbers of total cells, mastocytes, eosinophils (EOS), neutrophils, and lymphocytes. Enzyme-linked immunosorbent assay (ELISA) was adopted for the levels of immunoglobulin (IgE), IL-4, IL-5, IL-13 and interferon (IFN)-γ, flow cytometry for the percentages of IL-4 CD4 , IFN-γ CD4 and IFN-γ /IL-4 in total thymus-derived (T) cells, qRT-PCR for the mRNA expressions of IL-4, IL-5, IL-13, STAT6, pSTAT6, suppressor of cytokine signaling (SOCS), inducible nitric oxide synthase (iNOS) and vascular cell adhesion molecule (VCAM)-1, and Western blotting for the protein expressions of STAT6 and pSTAT6. RESULTS: Compared with the control group, the asthma group had irregular tissue structure and severe inflammation, increases in maximal pulmonary resistance, numbers of total cells, EOS, neutrophils, and lymphocytes, levels of IgE, IL-4, IL-5 and IL-13, percentages of IFN-γ CD4 and IFN-γ /IL-4 in total T cells, mRNA expressions of IL-4, IL-5, IL-13, STAT6, pSTAT6, SOCS, iNOS and VCAM-1, and protein expressions of STAT6 and pSTAT6, but decreases in IFN-γ level and percentage of IL-4 CD4 in total T cells. Compared with the asthma group, the IL-4R group had relatively regular tissue structure and light inflammation, declined maximal RL, numbers of total cells, EOS, neutrophils, and lymphocytes, contents of IgE, IL-4, IL-5 and IL-13, percentages of IFN-γ CD4 and IFN-γ /IL-4 in total T cells, mRNA expressions of IL-4, IL-5, IL-13, STAT6, pSTAT6, SOCS, iNOS and VCAM-1, and protein expressions of STAT6 and pSTAT6, but elevated IFN-γ content and percentage of IL-4 CD4 in total T cells. CONCLUSION: Our results demonstrate that IL-4R can suppress airway inflammation in bronchial asthma by inhibited the IL-4/STAT6 pathway, which may provide a new therapeutic approach for the treatment of bronchial asthma.
[Mh] Termos MeSH primário: Asma/fisiopatologia
Interleucina-4/metabolismo
Receptores de Interleucina-4/metabolismo
Fator de Transcrição STAT6/metabolismo
[Mh] Termos MeSH secundário: Animais
Western Blotting
Modelos Animais de Doenças
Ensaio de Imunoadsorção Enzimática
Eosinófilos/metabolismo
Inflamação/patologia
Linfócitos/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Neutrófilos/metabolismo
Óxido Nítrico Sintase Tipo II/metabolismo
Ovalbumina/administração & dosagem
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Molécula 1 de Adesão de Célula Vascular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Interleukin-4); 0 (STAT6 Transcription Factor); 0 (Vascular Cell Adhesion Molecule-1); 207137-56-2 (Interleukin-4); 9006-59-1 (Ovalbumin); EC 1.14.13.39 (Nitric Oxide Synthase Type II)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170118
[St] Status:MEDLINE


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[PMID]:28054352
[Au] Autor:Smolkova B; Tulinska J; Palkovicova Murinova L; Buocikova V; Liskova A; Rausova K; Kuricova M; Patayova H; Sustrova M; Neubauerova Svorcova E; Ilavska S; Szabova M; Nemessanyi T; Jahnova E; Dusinska M; Ciznar P; Fuortes L
[Ad] Endereço:Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
[Ti] Título:Impact of interleukin 13 (IL13) genetic polymorphism Arg130Gln on total serum immunoglobulin (IgE) levels and interferon (IFN)-γ gene expression.
[So] Source:Clin Exp Immunol;188(1):45-52, 2017 Apr.
[Is] ISSN:1365-2249
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:This cross-sectional study was designed to investigate the extent of genetic susceptibility by targeting variants in interleukin (IL)-4/IL-13 signalling pathways leading to atopic disease in early childhood. We evaluated involvement of five single nucleotide polymorphisms IL4 C-590T, IL13 C-1055T, IL13 Arg130Gln, IL4RA Ile50Val and IL4RA Gln576Arg, in the control of serum total and antigen-specific immunoglobulin (Ig)E levels. Furthermore, we analysed their association with changes in gene expression of five cytokines having key roles in inflammatory and anti-inflammatory immune response [IL-4, IL-13, interferon (IFN)-γ, IL-8 and IL-10]. Total and antigen-specific IgE levels in serum and gene expression of selected cytokines in peripheral blood were measured in 386 children aged 1-8 years. TaqMan allelic discrimination, amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and restriction fragment length polymorphisms (RFLP) methods validated by sequencing were used for genotyping. All genotypes for children with total and antigen-specific IgE levels in the normal range were in Hardy-Weinberg equilibrium. Gene expression analyses were carried out using TaqMan gene expression assays. We found elevated total IgE levels in carriers of IL13 Arg130Gln variant allele [odds ratio (OR) = 1·84; 95% confidence interval (CI) = 1·16-2·93]. This effect was more apparent for boys (OR = 2·31; 95% CI = 1·25-4·28). However, no significant association was observed for the other four variants examined. We found up-regulation of IFN-γ in children with elevated serum total IgE levels carrying the Arg130 allele (P = 0·005). No differences were found for IL4, IL8 or IL10, while IL13 gene expression was under the detection limit. IL13 Arg130Gln genotypes can play a role in genetic susceptibility to allergy via regulation of serum total IgE levels and affecting IFN-γ gene expression.
[Mh] Termos MeSH primário: Substituição de Aminoácidos
Códon
Expressão Gênica
Imunoglobulina E/sangue
Interferon gama/genética
Interleucina-13/genética
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Alelos
Criança
Pré-Escolar
Estudos Transversais
Feminino
Frequência do Gene
Estudos de Associação Genética
Predisposição Genética para Doença
Genótipo
Seres Humanos
Hipersensibilidade/sangue
Hipersensibilidade/epidemiologia
Hipersensibilidade/genética
Hipersensibilidade/imunologia
Imunoglobulina E/imunologia
Lactente
Masculino
Razão de Chances
Receptores de Interleucina-4/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Codon); 0 (Interleukin-13); 0 (Receptors, Interleukin-4); 37341-29-0 (Immunoglobulin E); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170508
[Lr] Data última revisão:
170508
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170106
[St] Status:MEDLINE
[do] DOI:10.1111/cei.12923



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