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Pesquisa : D12.776.260.108.500.061.750 [Categoria DeCS]
Referências encontradas : 289 [refinar]
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  1 / 289 MEDLINE  
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[PMID]:29324782
[Au] Autor:Shawki HH; Oishi H; Usui T; Kitadate Y; Basha WA; Abdellatif AM; Hasegawa K; Okada R; Mochida K; El-Shemy HA; Muratani M; Ogura A; Yoshida S; Takahashi S
[Ad] Endereço:Department of Anatomy and Embryology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan.
[Ti] Título:MAFB is dispensable for the fetal testis morphogenesis and the maintenance of spermatogenesis in adult mice.
[So] Source:PLoS One;13(1):e0190800, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The transcription factor MAFB is an important regulator of the development and differentiation of various organs and tissues. Previous studies have shown that MAFB is expressed in embryonic and adult mouse testes and is expected to act as the downstream target of retinoic acid (RA) to initiate spermatogenesis. However, its exact localization and function remain unclear. Here, we localized MAFB expression in embryonic and adult testes and analyzed its gene function using Mafb-deficient mice. We found that MAFB and c-MAF are the only large MAF transcription factors expressed in testes, while MAFA and NRL are not. MAFB was localized in Leydig and Sertoli cells at embryonic day (E) 18.5 but in Leydig cells, Sertoli cells, and pachytene spermatocytes in adults. Mafb-deficient testes at E18.5 showed fully formed seminiferous tubules with no abnormal structure or differences in testicular somatic cell numbers compared with those of control wild-type mice. Additionally, the expression levels of genes related to development and function of testicular cells were unchanged between genotypes. In adults, the expression of MAFB in Sertoli cells was shown to be stage specific and induced by RA. By generating Mafbfl/fl CAG-CreER™ (Mafb-cKO) mice, in which Cre recombinase was activated upon tamoxifen treatment, we found that the neonatal cKO mice died shortly upon Mafb deletion, but adult cKO mice were alive upon deletion. Adult cKO mice were fertile, and spermatogenesis maintenance was normal, as indicated by histological analysis, hormone levels, and germ cell stage-specific markers. Moreover, there were no differences in the proportion of seminiferous stages between cKO mice and controls. However, RNA-Seq analysis of cKO Sertoli cells revealed that the down-regulated genes were related to immune function and phagocytosis activity but not spermatogenesis. In conclusion, we found that MAFB is dispensable for fetal testis morphogenesis and spermatogenesis maintenance in adult mice, despite the significant gene expression in different cell types, but MAFB might be critical for phagocytosis activity of Sertoli cells.
[Mh] Termos MeSH primário: Fator de Transcrição MafB/metabolismo
Espermatogênese/fisiologia
Testículo/crescimento & desenvolvimento
Testículo/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Feminino
Fertilidade/fisiologia
Células Intersticiais do Testículo/citologia
Células Intersticiais do Testículo/metabolismo
Fator de Transcrição MafB/genética
Masculino
Camundongos Endogâmicos C57BL
Camundongos Knockout
Proteínas Proto-Oncogênicas c-maf/metabolismo
RNA Mensageiro/metabolismo
Células de Sertoli/citologia
Células de Sertoli/metabolismo
Espermatócitos/citologia
Espermatócitos/metabolismo
Testículo/anatomia & histologia
Testosterona/metabolismo
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Maf protein, mouse); 0 (MafB Transcription Factor); 0 (Mafb protein, mouse); 0 (Proto-Oncogene Proteins c-maf); 0 (RNA, Messenger); 3XMK78S47O (Testosterone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190800


  2 / 289 MEDLINE  
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[PMID]:28813657
[Au] Autor:Kang K; Park SH; Chen J; Qiao Y; Giannopoulou E; Berg K; Hanidu A; Li J; Nabozny G; Kang K; Park-Min KH; Ivashkiv LB
[Ad] Endereço:Graduate Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, NY 10021, USA; Arthritis and Tissue Degeneration Program and the David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY 10021, USA.
[Ti] Título:Interferon-γ Represses M2 Gene Expression in Human Macrophages by Disassembling Enhancers Bound by the Transcription Factor MAF.
[So] Source:Immunity;47(2):235-250.e4, 2017 Aug 15.
[Is] ISSN:1097-4180
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mechanisms by which interferon (IFN)-γ activates genes to promote macrophage activation are well studied, but little is known about mechanisms and functions of IFN-γ-mediated gene repression. We used an integrated transcriptomic and epigenomic approach to analyze chromatin accessibility, histone modifications, transcription-factor binding, and gene expression in IFN-γ-primed human macrophages. IFN-γ suppressed basal expression of genes corresponding to an "M2"-like homeostatic and reparative phenotype. IFN-γ repressed genes by suppressing the function of enhancers enriched for binding by transcription factor MAF. Mechanistically, IFN-γ disassembled a subset of enhancers by inducing coordinate suppression of binding by MAF, lineage-determining transcription factors, and chromatin accessibility. Genes associated with MAF-binding enhancers were suppressed in macrophages isolated from rheumatoid-arthritis patients, revealing a disease-associated signature of IFN-γ-mediated repression. These results identify enhancer inactivation and disassembly as a mechanism of IFN-γ-mediated gene repression and reveal that MAF regulates the macrophage enhancer landscape and is suppressed by IFN-γ to augment macrophage activation.
[Mh] Termos MeSH primário: Artrite Reumatoide/imunologia
Montagem e Desmontagem da Cromatina
Interferon gama/metabolismo
Macrófagos/imunologia
Proteínas Proto-Oncogênicas c-maf/metabolismo
[Mh] Termos MeSH secundário: Diferenciação Celular
Linhagem da Célula
Células Cultivadas
Citocinas/metabolismo
Elementos Facilitadores Genéticos/genética
Regulação da Expressão Gênica
Histonas/metabolismo
Seres Humanos
Ligação Proteica
Proteínas Proto-Oncogênicas c-maf/genética
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Histones); 0 (MAF protein, human); 0 (Proto-Oncogene Proteins c-maf); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170817
[St] Status:MEDLINE


  3 / 289 MEDLINE  
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[PMID]:28604806
[Au] Autor:Hooper KM; Kong W; Ganea D
[Ad] Endereço:Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America.
[Ti] Título:Prostaglandin E2 inhibits Tr1 cell differentiation through suppression of c-Maf.
[So] Source:PLoS One;12(6):e0179184, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prostaglandin E2 (PGE2), a major lipid mediator abundant at inflammatory sites, acts as a proinflammatory agent in models of inflammatory/autoimmune diseases by promoting CD4 Th1/Th17 differentiation. Regulatory T cells, including the IL-10 producing Tr1 cells counterbalance the proinflammatory activity of effector Th1/Th17 cells. Tr1 cell differentiation and function are induced by IL-27, and depend primarily on sustained expression of c-Maf in addition to AhR and Blimp-1. In agreement with the in vivo proinflammatory role of PGE2, here we report for the first time that PGE2 inhibits IL-27-induced differentiation and IL-10 production of murine CD4+CD49b+LAG-3+Foxp3- Tr1 cells. The inhibitory effect of PGE2 was mediated through EP4 receptors and induction of cAMP, leading to a significant reduction in c-Maf expression. Although PGE2 reduced IL-21 production in differentiating Tr1 cells, its inhibitory effect on Tr1 differentiation and c-Maf expression also occurred independent of IL-21 signaling. PGE2 did not affect STAT1/3 activation, AhR expression and only marginally reduced Egr-2/Blimp-1 expression. The effect of PGE2 on CD4+CD49b+LAG-3+ Tr1 differentiation was not associated with either induction of Foxp3 or IL-17 production, suggesting a lack of transdifferentiation into Foxp3+ Treg or effector Th17 cells. We recently reported that PGE2 inhibits the expression and production of IL-27 from activated conventional dendritic cells (cDC) in vivo and in vitro. The present study indicates that PGE2 also reduces murine Tr1 differentiation and function directly by acting on IL-27-differentiating Tr1 cells. Together, the ability of PGE2 to inhibit IL-27 production by cDC, and the direct inhibitory effect on Tr1 differentiation mediated through reduction in c-Maf expression, represent a new mechanistic perspective for the proinflammatory activity of PGE2.
[Mh] Termos MeSH primário: Diferenciação Celular/efeitos dos fármacos
Dinoprostona/farmacologia
Proteínas Proto-Oncogênicas c-maf/antagonistas & inibidores
Linfócitos T Reguladores/citologia
Linfócitos T Reguladores/efeitos dos fármacos
Linfócitos T Reguladores/metabolismo
[Mh] Termos MeSH secundário: Animais
AMP Cíclico
Interleucina-27/metabolismo
Interleucinas/metabolismo
Camundongos
Camundongos Knockout
Receptores de Antígenos de Linfócitos T/metabolismo
Receptores de Prostaglandina E Subtipo EP4/metabolismo
Fator de Transcrição STAT1/metabolismo
Fator de Transcrição STAT3/metabolismo
Transdução de Sinais
Subpopulações de Linfócitos T/citologia
Subpopulações de Linfócitos T/efeitos dos fármacos
Subpopulações de Linfócitos T/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukin-27); 0 (Interleukins); 0 (Proto-Oncogene Proteins c-maf); 0 (Receptors, Antigen, T-Cell); 0 (Receptors, Prostaglandin E, EP4 Subtype); 0 (STAT1 Transcription Factor); 0 (STAT3 Transcription Factor); 0 (interleukin-21); E0399OZS9N (Cyclic AMP); K7Q1JQR04M (Dinoprostone)
[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:170613
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179184


  4 / 289 MEDLINE  
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[PMID]:28502899
[Au] Autor:Shi L; Wang M; Zhang Y; Shen G; Di H; Wang Y; He L
[Ad] Endereço:Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400716, China.
[Ti] Título:The expression of P450 genes mediating fenpropathrin resistance is regulated by CncC and Maf in Tetranychus cinnabarinus (Boisduval).
[So] Source:Comp Biochem Physiol C Toxicol Pharmacol;198:28-36, 2017 Aug.
[Is] ISSN:1532-0456
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although overexpression of genes encoding detoxification enzymes is a well-known mechanism of pesticide resistance of mites, the regulators involved in this process are still illiterate. Previous studies in our laboratory demonstrated that the overexpression of six P450 genes contributes to fenpropathrin resistance in T. cinnabarinus. In this study, six transcription factor genes that likely regulate the expression of P450 genes were identified and characterized. Quantitative PCR (qPCR) analysis showed that three transcription factor genes were highly expressed in a fenpropathrin-resistant (FeR) strain of T. cinnabarinus. The cap 'n' collar isoform C (CncC) and muscle aponeurosis fibromatosis (Maf) family transcription factors were identified as the key regulator of P450 genes by RNA interference (RNAi). Furthermore, research on the promoters of these P450 genes using reporter assays identified that CncC and Maf influence the susceptibility of T. cinnabarinus to fenpropathrin through regulating the expression of P450 genes. This study increases our understanding of the molecular mechanisms underlying the regulation of P450 genes involved in detoxification of acaricides in T. cinnabarinus.
[Mh] Termos MeSH primário: Proteínas de Artrópodes/genética
Resistência a Inseticidas/genética
Piretrinas/farmacologia
Tetranychidae/efeitos dos fármacos
Tetranychidae/genética
[Mh] Termos MeSH secundário: Animais
Sistema Enzimático do Citocromo P-450/genética
Regulação da Expressão Gênica/efeitos dos fármacos
Inativação Metabólica/efeitos dos fármacos
Resistência a Inseticidas/efeitos dos fármacos
Regiões Promotoras Genéticas
Proteínas Proto-Oncogênicas c-maf/genética
Interferência de RNA
Proteínas Repressoras/genética
Fatores de Transcrição/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arthropod Proteins); 0 (Proto-Oncogene Proteins c-maf); 0 (Pyrethrins); 0 (Repressor Proteins); 0 (Transcription Factors); 87BH96P0MX (fenpropathrin); 9035-51-2 (Cytochrome P-450 Enzyme System)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170728
[Lr] Data última revisão:
170728
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE


  5 / 289 MEDLINE  
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[PMID]:28323940
[Au] Autor:Bos MM; Smit RAJ; Trompet S; van Heemst D; Noordam R
[Ad] Endereço:Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
[Ti] Título:Thyroid Signaling, Insulin Resistance, and 2 Diabetes Mellitus: A Mendelian Randomization Study.
[So] Source:J Clin Endocrinol Metab;102(6):1960-1970, 2017 Jun 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Increasing evidence suggests an association between thyroid-stimulating hormone (TSH), free thyroxine (fT4), and deiodinases with insulin resistance and type 2 diabetes mellitus (T2D). Objective: We examined whether TSH and fT4 levels and deiodinases are causally associated with insulin resistance and T2D, using Mendelian randomization. Methods: We selected 20 genetic variants for TSH level and four for fT4 level (identified in a genome-wide association study (GWAS) meta-analysis of European-ancestry cohorts) as instrumental variables for TSH and fT4 levels, respectively. We used summary data from GWASs on the outcomes T2D [Diabetes, Genetics Replication and Meta-analysis (DIAGRAM), n = 12,171 cases and n = 56,862 control subjects] and glycemic traits in patients without diabetes [Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC), n = 46,186 for fasting glucose and insulin and n = 46,368 for hemoglobin A1c]. To examine whether the associations between TSH/fT4 levels and the study outcomes were causal, we combined the effects of the genetic instruments. Furthermore, we examined the associations among 16 variants in DIO1, DIO2, DIO3, and T2D and glycemic traits. Results: We found no evidence for an association between the combined genetic instrumental variables for TSH and fT4 and the study outcomes. For example, we did not observe a genetically determined association between high TSH level and T2D (odds ratio, 0.91 per standard deviation TSH increase; 95% confidence interval, 0.78 to 1.07). Selected genetic variants in DIO1 (e.g., rs7527713) were associated with measures of insulin resistance. Conclusion: We found no evidence for a causal association between circulatory levels of TSH and fT4 with insulin resistance and T2D, but we found suggestive evidence that DIO1 affects glucose metabolism.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/genética
Resistência à Insulina/genética
Tireotropina/metabolismo
Tiroxina/metabolismo
[Mh] Termos MeSH secundário: Alelos
Glicemia/metabolismo
Bases de Dados Factuais
Diabetes Mellitus Tipo 2/metabolismo
Variação Genética
Estudo de Associação Genômica Ampla
Hemoglobina A Glicada/metabolismo
Seres Humanos
Insulina/metabolismo
Iodeto Peroxidase/genética
Análise da Randomização Mendeliana
Razão de Chances
Polimorfismo de Nucleotídeo Único
Proteínas Proto-Oncogênicas c-maf/genética
Fator A de Crescimento do Endotélio Vascular/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Glycated Hemoglobin A); 0 (Insulin); 0 (MAF protein, human); 0 (Proto-Oncogene Proteins c-maf); 0 (VEGFA protein, human); 0 (Vascular Endothelial Growth Factor A); 0 (hemoglobin A1c protein, human); 9002-71-5 (Thyrotropin); EC 1.11.1.- (iodothyronine deiodinase type I); EC 1.11.1.- (iodothyronine deiodinase type II); EC 1.11.1.- (iodothyronine deiodinase type III); EC 1.11.1.8 (Iodide Peroxidase); Q51BO43MG4 (Thyroxine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2016-2816


  6 / 289 MEDLINE  
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[PMID]:28300844
[Au] Autor:Chang KK; Liu LB; Jin LP; Zhang B; Mei J; Li H; Wei CY; Zhou WJ; Zhu XY; Shao J; Li DJ; Li MQ
[Ad] Endereço:Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200011, People's Republic of China.
[Ti] Título:IL-27 triggers IL-10 production in Th17 cells via a c-Maf/RORγt/Blimp-1 signal to promote the progression of endometriosis.
[So] Source:Cell Death Dis;8(3):e2666, 2017 Mar 16.
[Is] ISSN:2041-4889
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Endometriosis is an estrogen-dependent inflammatory disease. The anti-inflammatory cytokine IL-10 is also increased in endometriosis. IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. However, the mechanism of inducing IL-10-producing Th17 cells is still largely unknown. The present study investigated the differentiation mechanism and role of IL-10-producing Th17 cells in endometriosis. Here, we report that IL-10 Th17 cells are significantly increased in the peritoneal fluid of women with endometriosis, along with an elevation of IL-27, IL-6 and TGF-ß. Compared with peripheral CD4 T cells, endometrial CD4 T cells highly expressed IL-27 receptors, especially the ectopic endometrium. Under external (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and local (estrogen, IL-6 and TGF-ß) environmental regulation, IL-27 from macrophages and endometrial stromal cells (ESCs) induces IL-10 production in Th17 cells in vitro and in vivo. This process may be mediated through the interaction between c-musculoaponeurotic fibrosarconna (c-Maf) and retinoic acid-related orphan receptor gamma t (RORγt), and associated with the upregulation of downstream B lymphocyte-induced maturation protein-1 (Blimp-1). IL-10 Th17 cells, in turn, stimulate the proliferation and implantation of ectopic lesions and accelerate the progression of endometriosis. These results suggest that IL-27 is a pivotal regulator in endometriotic immune tolerance by triggering Th17 cells to produce IL-10 and promoting the rapid growth and implantation of ectopic lesions. This finding provides a scientific basis for potential therapeutic strategies aimed at preventing the development of endometriosis, especially for patients with high levels of IL-10 Th17 cells.
[Mh] Termos MeSH primário: Endometriose/metabolismo
Interleucina-10/metabolismo
Interleucinas/metabolismo
Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo
Proteínas Proto-Oncogênicas c-maf/metabolismo
Proteínas Repressoras/metabolismo
Células Th17/metabolismo
[Mh] Termos MeSH secundário: Adulto
Linfócitos T CD4-Positivos/metabolismo
Linfócitos T CD4-Positivos/patologia
Diferenciação Celular/fisiologia
Progressão da Doença
Endometriose/patologia
Endométrio/metabolismo
Endométrio/patologia
Feminino
Seres Humanos
Interleucina-6/metabolismo
Macrófagos/metabolismo
Macrófagos/patologia
Fator 1 de Ligação ao Domínio I Regulador Positivo
Células Estromais/metabolismo
Células Estromais/patologia
Fator de Crescimento Transformador beta/metabolismo
Regulação para Cima/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IL10 protein, human); 0 (IL27 protein, human); 0 (Interleukin-6); 0 (Interleukins); 0 (MAF protein, human); 0 (Nuclear Receptor Subfamily 1, Group F, Member 3); 0 (Proto-Oncogene Proteins c-maf); 0 (RORC protein, human); 0 (Repressor Proteins); 0 (Transforming Growth Factor beta); 130068-27-8 (Interleukin-10); 138415-26-6 (PRDM1 protein, human); EC 2.1.1.- (Positive Regulatory Domain I-Binding Factor 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE
[do] DOI:10.1038/cddis.2017.95


  7 / 289 MEDLINE  
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[PMID]:28235765
[Au] Autor:Tsukamoto H; Fujieda K; Hirayama M; Ikeda T; Yuno A; Matsumura K; Fukuma D; Araki K; Mizuta H; Nakayama H; Senju S; Nishimura Y
[Ad] Endereço:Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto, Japan. htsukamo@kumamoto-u.ac.jp mxnishim@gpo.kumamoto-u.ac.jp.
[Ti] Título:Soluble IL6R Expressed by Myeloid Cells Reduces Tumor-Specific Th1 Differentiation and Drives Tumor Progression.
[So] Source:Cancer Res;77(9):2279-2291, 2017 May 01.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:IL6 produced by tumor cells promotes their survival, conferring a poor prognosis in patients with cancer. IL6 also contributes to immunosuppression of CD4 T cell-mediated antitumor effects. In this study, we focused on the impact of IL6 trans-signaling mediated by soluble IL6 receptors (sIL6R) expressed in tumor-bearing hosts. Higher levels of sIL6R circulating in blood were observed in tumor-bearing mice, whereas the systemic increase of sIL6R was not prominent in tumor-bearing mice with myeloid cell-specific conditional deletion of IL6R even when tumor cells produced sIL6R. Abundant sIL6R was released by CD11b cells from tumor-bearing mice but not tumor-free mice. Notably, IL6-mediated defects in Th1 differentiation, T-cell helper activity for tumor-specific CD8 T cells, and downstream antitumor effects were rescued by myeloid-specific deletion of sIL6R. Expression of the T-cell transcription factor c-Maf was upregulated in CD4 T cells primed in tumor-bearing mice in an IL6-dependent manner. Investigations with c-Maf loss-of-function T cells revealed that c-Maf activity was responsible for IL6/sIL6R-induced Th1 suppression and defective T-cell-mediated antitumor responses. In patients with cancer, myeloid cell-derived sIL6R was also possibly associated with Th1 suppression and c-Maf expression. Our results argued that increased expression of sIL6R from myeloid cells and subsequent c-Maf induction were adverse events for counteracting tumor-specific Th1 generation. Overall, this work provides a mechanistic rationale for sIL6R targeting to improve the efficacy of T-cell-mediated cancer immunotherapy. .
[Mh] Termos MeSH primário: Carcinogênese/genética
Interleucina-6/genética
Neoplasias/genética
Proteínas Proto-Oncogênicas c-maf/genética
[Mh] Termos MeSH secundário: Animais
Linfócitos T CD4-Positivos/patologia
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Camundongos
Terapia de Alvo Molecular
Células Mieloides/metabolismo
Células Mieloides/patologia
Neoplasias/patologia
Receptores de Interleucina-6/genética
Células Th1
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IL6 protein, human); 0 (Interleukin-6); 0 (MAF protein, human); 0 (Proto-Oncogene Proteins c-maf); 0 (Receptors, Interleukin-6)
[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:170226
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-16-2446


  8 / 289 MEDLINE  
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[PMID]:27793878
[Au] Autor:Qiang YW; Ye S; Chen Y; Buros AF; Edmonson R; van Rhee F; Barlogie B; Epstein J; Morgan GJ; Davies FE
[Ad] Endereço:Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR.
[Ti] Título:MAF protein mediates innate resistance to proteasome inhibition therapy in multiple myeloma.
[So] Source:Blood;128(25):2919-2930, 2016 Dec 22.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Multiple myeloma (MM) patients with the t(14;16) translocation have a poor prognosis, and unlike other molecular subgroups, their outcome has not improved with the introduction of bortezomib (Bzb). The mechanism underlying innate resistance of MM to Bzb is unknown. In the present study, we have investigated how MAF overexpression impacts resistance to proteasome inhibitor (PI) therapy (Bzb and carfilzomib). High levels of MAF protein were found in t(14;16) cell lines; cell lines from the t(4;14) subgroup had intermediate levels, whereas cell lines from the other subgroups had low levels. High expression of MAF protein in t(14;16) was associated with significantly higher PI half-maximum inhibitory concentration values compared with other molecular subgroups. PI exposure abrogated glycogen synthase kinase 3ß (GSK3ß)-mediated degradation of MAF protein, resulting in increased MAF protein stability and PI resistance. Subsequent studies using loss-of-function and gain-of-function models showed that silencing MAF led to increased sensitivity to PIs, enhanced apoptosis, and activation of caspase-3, -7, -8, -9, poly (ADP-ribose) polymerase, and lamin A/C. In contrast, overexpression of MAF resulted in increased resistance to PIs and reduced apoptosis. These results define the role of MAF and GSK3 in the resistance of t(14;16) MM to PIs and identifies a novel mechanism by which MAF protein levels are regulated by PIs, which in turn confers resistance to PIs.
[Mh] Termos MeSH primário: Resistência a Medicamentos Antineoplásicos
Imunidade Inata
Mieloma Múltiplo/tratamento farmacológico
Mieloma Múltiplo/metabolismo
Inibidores de Proteassoma/uso terapêutico
Proteínas Proto-Oncogênicas c-maf/metabolismo
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Caspases/metabolismo
Linhagem Celular Tumoral
Cromossomos Humanos Par 14/genética
Cromossomos Humanos Par 16/genética
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Ativação Enzimática/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Inativação Gênica/efeitos dos fármacos
Glicogênio Sintase Quinase 3 beta/metabolismo
Seres Humanos
Imunidade Inata/efeitos dos fármacos
Laminas/metabolismo
Mieloma Múltiplo/genética
Mieloma Múltiplo/patologia
Fosforilação/efeitos dos fármacos
Poli(ADP-Ribose) Polimerases/metabolismo
Prognóstico
Inibidores de Proteassoma/farmacologia
Proteólise/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-maf/genética
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Translocação Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lamins); 0 (MAF protein, human); 0 (Proteasome Inhibitors); 0 (Proto-Oncogene Proteins c-maf); 0 (RNA, Messenger); EC 2.4.2.30 (Poly(ADP-ribose) Polymerases); EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta); EC 3.4.22.- (Caspases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161030
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2016-03-706077


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[PMID]:27596755
[Au] Autor:Pathania M; Wang Y; Simirskii VN; Duncan MK
[Ad] Endereço:Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
[Ti] Título:ß1-integrin controls cell fate specification in early lens development.
[So] Source:Differentiation;92(4):133-147, 2016 Oct - Nov.
[Is] ISSN:1432-0436
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Integrins are heterodimeric cell surface molecules that mediate cell-extracellular matrix (ECM) adhesion, ECM assembly, and regulation of both ECM and growth factor induced signaling. However, the developmental context of these diverse functions is not clear. Loss of ß1-integrin from the lens vesicle (mouse E10.5) results in abnormal exit of anterior lens epithelial cells (LECs) from the cell cycle and their aberrant elongation toward the presumptive cornea by E12.5. These cells lose expression of LEC markers and initiate expression of the Maf (also known as c-Maf) and Prox1 transcription factors as well as other lens fiber cell markers. ß1-integrin null LECs also upregulate the ERK, AKT and Smad1/5/8 phosphorylation indicative of BMP and FGF signaling. By E14.5, ß1-integrin null lenses have undergone a complete conversion of all lens epithelial cells into fiber cells. These data suggest that shortly after lens vesicle closure, ß1-integrin blocks inappropriate differentiation of the lens epithelium into fibers, potentially by inhibiting BMP and/or FGF receptor activation. Thus, ß1-integrin has an important role in fine-tuning the response of the early lens to the gradient of growth factors that regulate lens fiber cell differentiation.
[Mh] Termos MeSH primário: Diferenciação Celular/genética
Proteínas de Homeodomínio/biossíntese
Integrina beta1/genética
Cristalino/metabolismo
Organogênese/genética
Proteínas Supressoras de Tumor/biossíntese
[Mh] Termos MeSH secundário: Animais
Adesão Celular/genética
Epitélio/crescimento & desenvolvimento
Epitélio/metabolismo
Matriz Extracelular/genética
Matriz Extracelular/metabolismo
Regulação da Expressão Gênica no Desenvolvimento
Proteínas de Homeodomínio/genética
Integrina beta1/metabolismo
Cristalino/crescimento & desenvolvimento
Camundongos
Proteínas Proto-Oncogênicas c-maf/biossíntese
Proteínas Proto-Oncogênicas c-maf/genética
Transdução de Sinais
Proteínas Supressoras de Tumor/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Homeodomain Proteins); 0 (Integrin beta1); 0 (Maf protein, mouse); 0 (Proto-Oncogene Proteins c-maf); 0 (Tumor Suppressor Proteins); 0 (prospero-related homeobox 1 protein)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160907
[St] Status:MEDLINE


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[PMID]:27108804
[Au] Autor:Davudian S; Mansoori B; Shajari N; Mohammadi A; Baradaran B
[Ad] Endereço:Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
[Ti] Título:BACH1, the master regulator gene: A novel candidate target for cancer therapy.
[So] Source:Gene;588(1):30-7, 2016 Aug 15.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACH1 (BTB and CNC homology 1, basic leucine zipper transcription factor 1) is a transcriptional factor and a member of cap 'n' collar (CNC) and basic region leucine zipper factor family. In contrast to other bZIP family members, BACH1 appeared as a comparatively specific transcription factor. It acts as transcription regulator and is recognized as a recently hypoxia regulator and functions as an inducible repressor for the HO-1 gene in many human cell types in response to stress oxidative. In regard to studies lately, although, BACH1 has been related to the regulation of oxidative stress and heme oxidation, it has never been linked to invasion and metastasis. Recent studies have showed that BACH1 is involved in bone metastasis of breast cancer by up-regulating vital metastatic genes like CXCR4 and MMP1. This newly discovered aspect of BACH1 gene provides new insight into cancer progression study and stands on its master regulator role in metastasis process, raising the possibility of considering it as a potential target for cancer therapy.
[Mh] Termos MeSH primário: Fatores de Transcrição de Zíper de Leucina Básica/genética
Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/patologia
Proteínas de Grupos de Complementação da Anemia de Fanconi/genética
[Mh] Termos MeSH secundário: Animais
Fatores de Transcrição de Zíper de Leucina Básica/antagonistas & inibidores
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo
Neoplasias Ósseas/secundário
Neoplasias da Mama/genética
Neoplasias da Mama/metabolismo
Movimento Celular
Proteínas de Grupos de Complementação da Anemia de Fanconi/antagonistas & inibidores
Proteínas de Grupos de Complementação da Anemia de Fanconi/metabolismo
Heme Oxigenase-1/genética
Seres Humanos
Terapia de Alvo Molecular
Metástase Neoplásica
Estresse Oxidativo
Proteínas Proto-Oncogênicas c-maf/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (BACH1 protein, human); 0 (Basic-Leucine Zipper Transcription Factors); 0 (Fanconi Anemia Complementation Group Proteins); 0 (MAF protein, human); 0 (Proto-Oncogene Proteins c-maf); EC 1.14.14.18 (HMOX1 protein, human); EC 1.14.14.18 (Heme Oxygenase-1)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170123
[Lr] Data última revisão:
170123
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160426
[St] Status:MEDLINE



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