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[PMID]: 28942284 [Au] Autor: Yan Y; Song D; Liu L; Meng X; Qi C; Wang J [Ad] Endereço: Department of Cardiology, The Second Hospital, Jilin University, No. 218 Ziqiang Street, Changchun 130041, China. [Ti] Título: The relationship of plasma decoy receptor 3 and coronary collateral circulation in patients with coronary artery disease. [So] Source: Life Sci;189:84-88, 2017 Nov 15. [Is] ISSN: 1879-0631 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: OBJECTIVE: Previously, decoy receptor 3 (DcR3) was found to be a potential angiogenetic factor, while the relationship of DcR3 with coronary collateral circulation formation has not been investigated. In this study, we aimed to investigate whether plasma decoy receptor 3 levels was associated with CCC formation and evaluate its predictive power for CCC status in patients with coronary artery disease. METHODS: Among patients who underwent coronary angiography with coronary artery disease and had a stenosis of ≥90% were included in our study. Collateral degree was graded according to Rentrope Cohen classification. Patients with grade 2 or 3 collateral degree were enrolled in good CCC group and patients with grade 0 or 1 collateral degree were enrolled in poor CCC group. RESULTS: Plasma DcR3 level was significantly higher in good CCC group (328.00±230.82 vs 194.84±130.63ng/l, p<0.01) and positively correlated with Rentrope grade (p<0.01). In addition, plasma DcR3 was also positively correlated with VEGF-A. Both ROC (receiver operating characteristic curve) and multinomial logistical regression analysis showed that plasma DcR3 displayed potent predictive power for CCC status. CONCLUSIONS: Higher plasma DcR3 level was related to better CCC formation and displayed potent predictive power for CCC status. [Mh] Termos MeSH primário: Circulação Colateral/fisiologia Doença da Artéria Coronariana/fisiopatologia Estenose Coronária/fisiopatologia Membro 6b de Receptores do Fator de Necrose Tumoral/sangue [Mh] Termos MeSH secundário: Idoso Angiografia Coronária Feminino Seres Humanos Modelos Logísticos Masculino Meia-Idade Valor Preditivo dos Testes Fator A de Crescimento do Endotélio Vascular/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Receptors, Tumor Necrosis Factor, Member 6b); 0 (TNFRSF6B protein, human); 0 (Vascular Endothelial Growth Factor A) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171023 [Lr] Data última revisão: 171023 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170925 [St] Status: MEDLINE

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[PMID]: 28223726 [Au] Autor: Chen J; Guo XZ; Li HY; Zhao JJ; Xu WD [Ad] Endereço: Jiang Chen, Xiao-Zhong Guo, Hong-Yu Li, Jia-Jun Zhao, Wen-Da Xu, Department of Gastroenterology, Shenyang General Hospital of PLA, Shenyang 110016, Liaoning Province, China. [Ti] Título: Dendritic cells engineered to secrete anti-DcR3 antibody augment cytotoxic T lymphocyte response against pancreatic cancer . [So] Source: World J Gastroenterol;23(5):817-829, 2017 Feb 07. [Is] ISSN: 2219-2840 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: AIM: To investigate the enhanced cytotoxic T lymphocyte responses against pancreatic cancer (PC) induced by dendritic cells (DCs) engineered to secrete anti-DcR3 monoclonal antibody (mAb). METHODS: DCs, T lymphocytes and primary PC cells were obtained from PC patients. DCs were transfected with a designed humanized anti-DcR3 monoclonal antibody heavy and light chain mRNA and/or total tumor RNA (DC-tumor-anti-DcR3 RNA or DC-total tumor RNA) by using electroporation technology. The identification, concentration and function of anti-DcR3 mAb secreted by DC-tumor-anti-DcR3 RNA were determined by western blotting and enzyme-linked immunosorbent assay. After co-culturing of autologous isolated PC cells with target DCs, the effects of secreting anti-DcR3 mAb on RNA-DCs' viability and apoptosis were assessed by MTT assay and flow cytometry. Analysis of enhanced antigen-specific immune response against PC induced by anti-DcR3 mAb secreting DCs was performed using a Cr releasing test. T cell responses induced by RNA-loaded DCs were analyzed by measuring cytokine levels, including IFN-γ, IL-10, IL4, TNF-α and IL-12. RESULTS: The anti-DcR3 mAb secreted by DCs reacted with recombinant human DcR3 protein and generated a band with 35 kDa molecular weight. The secreting mAb was transient, peaking at 24 h and becoming undetectable after 72 h. After co-incubation with DC-tumor-anti-DcR3 RNA for designated times, the DcR3 level in the supernatant of autologous PC cells was significantly down-regulated ( < 0.05). DCs secreting anti-DcR3 mAb could improve cell viability and slow down the apoptosis of RNA-loaded DCs, compared with DC-total tumor RNA ( < 0.01). The anti-DcR3 mAb secreted by DC-tumor-anti-DcR3 RNA could enhance the induction of cytotoxic T lymphocytes (CTLs) activity toward RNA-transfected DCs, primary tumor cells, and PC cell lines, compared with CTLs stimulated by DC-total tumor RNA or control group ( < 0.05). Meanwhile, the antigen-specific CTL responses were MHC class I-restricted. The CD4+ T cells and CD8+ T cells incubated with anti-DcR3 mAb secreting DCs could produce extremely higher level IFN-γ and lower level IL4 than those incubated with DC-total tumor RNA or controls ( < 0.01). CONCLUSION: DCs engineered to secrete anti-DcR3 antibody can augment CTL responses against PC , and the immune-enhancing effects may be partly due to their capability of down-regulating DC apoptosis and adjusting the Th1/Th2 cytokine network. [Mh] Termos MeSH primário: Células Dendríticas/imunologia Neoplasias Pancreáticas/imunologia Neoplasias Pancreáticas/terapia Membro 6b de Receptores do Fator de Necrose Tumoral/imunologia Linfócitos T Citotóxicos/imunologia [Mh] Termos MeSH secundário: Adulto Idoso Anticorpos Monoclonais/uso terapêutico Vacinas Anticâncer/imunologia Vacinas Anticâncer/uso terapêutico Linhagem Celular Tumoral Feminino Seres Humanos Imunoterapia Adotiva Técnicas In Vitro Masculino Meia-Idade Células Tumorais Cultivadas [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies, Monoclonal); 0 (Cancer Vaccines); 0 (Receptors, Tumor Necrosis Factor, Member 6b); 0 (TNFRSF6B protein, human) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170807 [Lr] Data última revisão: 170807 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170223 [St] Status: MEDLINE [do] DOI: 10.3748/wjg.v23.i5.817

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[PMID]: 27665176 [Au] Autor: Bamias G; Filidou E; Goukos D; Valatas V; Arvanitidis K; Panagopoulou M; Kouklakis G; Daikos GL; Ladas SD; Kolios G [Ad] Endereço: Academic Department of Gastroenterology, Laiko Hospital, Medical School of National and Kapodistrian University of Athens, University of Athens, Athens, Greece. Electronic address: gbamias@gmail.com. [Ti] Título: Crohn's disease-associated mucosal factors regulate the expression of TNF-like cytokine 1A and its receptors in primary subepithelial intestinal myofibroblasts and intestinal epithelial cells. [So] Source: Transl Res;180:118-130.e2, 2017 Feb. [Is] ISSN: 1878-1810 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Intestinal subepithelial myofibroblasts (SEMFs) exert a profibrotic role in Crohn's disease (CD). Tumor necrosis factor-like cytokine 1A (TL1A) and its receptors, death-domain receptor 3 (DR3) and decoy receptor 3 (DcR3), are mucosal factors with significant involvement in experimental inflammation and CD. We aimed to determine the regulation of expression of this system of proteins in SEMFs and intestinal epithelial cells. The relative amount of mRNA transcripts for TL1A, DR3, and DcR3 was measured by real-time reverse transcription polymerase chain reaction in cultured primary SEMFs, colonic myofibroblast cell line 18CO, and epithelial cell line HT29. Protein expression was determined by immunofluorescence. The effect of various proinflammatory stimuli in mRNA and protein expression was studied. TL1A mRNA and protein expression in primary SEMFs (and 18CO cells) was significantly upregulated after stimulation with interleukin 1-alpha and/or tumor necrosis factor alpha (TNF-α) (32- to 44-fold increase, P < 0.05 vs unstimulated). Following stimulation with interleukin 1-alpha + TNF-α + IFN-γ, HT-29 cells highly expressed DR3 (4.1-fold over unstimulated, P = 0.008) and DcR3 (56-fold, P = 0.009) and secreted soluble factors that led to induction of TL1A mRNA in primary SEMFs (28-fold, P = 0.008). Activated epithelial cells significantly upregulated IL-8 expression in response to stimulation with recombinant TL1A. Supernatants from mucosal cultures of patients with CD were able to stimulate the expression of TL1A in cultured primary SEMFs, in comparison to supernatants from healthy controls (3.8-fold increase, P < 0.05) or culture media alone (P < 0.05). In conclusion, we found that proinflammatory cytokines are important regulators of the expression of TL1A in SEMFs and of its receptors in intestinal epithelial cells. Our results raise the possibility for involvement of TL1A/DR3/DR3-mediated mechanisms in epithelial-mesenchymal interactions and the development of inflammation-induced intestinal fibrosis in CD. [Mh] Termos MeSH primário: Doença de Crohn/metabolismo Células Epiteliais/metabolismo Mucosa Intestinal/metabolismo Miofibroblastos/metabolismo Membro 25 de Receptores de Fatores de Necrose Tumoral/metabolismo Membro 6b de Receptores do Fator de Necrose Tumoral/metabolismo [Mh] Termos MeSH secundário: Células Epiteliais/efeitos dos fármacos Células Epiteliais/patologia Células HT29 Seres Humanos Mediadores da Inflamação/farmacologia Interleucina-8/genética Interleucina-8/metabolismo Mucosa Intestinal/efeitos dos fármacos Mucosa Intestinal/patologia Miofibroblastos/efeitos dos fármacos Miofibroblastos/patologia RNA Mensageiro/genética RNA Mensageiro/metabolismo Solubilidade Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Inflammation Mediators); 0 (Interleukin-8); 0 (RNA, Messenger); 0 (Receptors, Tumor Necrosis Factor, Member 25); 0 (Receptors, Tumor Necrosis Factor, Member 6b); 0 (TNFRSF25 protein, human); 0 (TNFRSF6B protein, human); 0 (TNFSF15 protein, human); 0 (Tumor Necrosis Factor Ligand Superfamily Member 15) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170626 [Lr] Data última revisão: 170626 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 160926 [St] Status: MEDLINE

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[PMID]: 26911723 [Au] Autor: Chen MH; Kan HT; Liu CY; Yu WK; Lee SS; Wang JH; Hsieh SL [Ad] Endereço: Department of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Allergy, Immunology and Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. [Ti] Título: Serum decoy receptor 3 is a biomarker for disease severity in nonatopic asthma patients. [So] Source: J Formos Med Assoc;116(1):49-56, 2017 Jan. [Is] ISSN: 0929-6646 [Cp] País de publicação: Singapore [La] Idioma: eng [Ab] Resumo: BACKGROUND/PURPOSE: Decoy receptor 3 (DcR3), a soluble receptor of the tumor necrosis factor receptor superfamily, is a pleiotropic immunomodulator. The aim of this study was to investigate serum DcR3 levels in atopic and nonatopic asthma patients. METHODS: The serum DcR3 levels of 70 adults with asthma and 20 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). The asthma patients were divided into atopic and nonatopic subgroups, based on the presence or absence of immunoglobulin E (IgE) specific to allergen. Correlations between serum DcR3 levels and blood total-eosinophil counts, forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), and Asthma Control Test (ACT) scores were analyzed. RESULTS: The mean serum DcR3 level was significantly higher in asthma patients than in healthy controls (266.1 ± 60.6 pg/mL vs. 63.7 ± 21.9 pg/mL, p = 0.003), but there was no significant difference between the mean serum DcR3 level of asthma patients with atopy (37 patients) and patients without atopy (33 patients; 298.7 ± 111.2 pg/mL vs. 230.6 ± 38.5 pg/mL, p = 0.064). However, the serum DcR3 level was positively correlated with the total eosinophil count (r = 0.448, p = 0.012) and inversely correlated with the percentages of predicted FEV1, FEV1/FVC, and ACT score (r = 0.409, p = 0.018; r = -0.399, p = 0.021; and r = -0.505, p = 0.003, respectively) in nonatopic asthma patients, but not in atopic patients. CONCLUSION: High serum DcR3 levels are associated with disease severity in nonatopic asthma patients, which suggests that DcR3 is a potential biomarker that can be used to predict the severity of nonatopic asthma. [Mh] Termos MeSH primário: Asma/sangue Imunoglobulina E/sangue Membro 6b de Receptores do Fator de Necrose Tumoral/sangue [Mh] Termos MeSH secundário: Adulto Idoso Biomarcadores/sangue Estudos de Casos e Controles Ensaio de Imunoadsorção Enzimática Feminino Seres Humanos Contagem de Leucócitos Masculino Meia-Idade Testes de Função Respiratória Índice de Gravidade de Doença Taiwan [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Biomarkers); 0 (Receptors, Tumor Necrosis Factor, Member 6b); 0 (TNFRSF6B protein, human); 37341-29-0 (Immunoglobulin E) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170825 [Lr] Data última revisão: 170825 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160226 [St] Status: MEDLINE

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[PMID]: 27806260 [Au] Autor: Liu W; Ramagopal U; Cheng H; Bonanno JB; Toro R; Bhosle R; Zhan C; Almo SC [Ad] Endereço: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA; Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. [Ti] Título: Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3. [So] Source: Structure;24(11):2016-2023, 2016 Nov 01. [Is] ISSN: 1878-4186 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The apoptotic effect of FasL:Fas signaling is disrupted by DcR3, a unique secreted member of the tumor necrosis factor receptor superfamily, which also binds and neutralizes TL1A and LIGHT. DcR3 is highly elevated in patients with various tumors and contributes to mechanisms by which tumor cells to evade host immune surveillance. Here we report the crystal structure of FasL in complex with DcR3. Comparison of FasL:DcR3 structure with our earlier TL1A:DcR3 and LIGHT:DcR3 structures supports a paradigm involving the recognition of invariant main-chain and conserved side-chain functionalities, which is responsible for the recognition of multiple TNF ligands exhibited by DcR3. The FasL:DcR3 structure also provides insight into the FasL:Fas recognition surface. We demonstrate that the ability of recombinant FasL to induce Jurkat cell apoptosis is significantly enhanced by native glycosylation or by structure-inspired mutations, both of which result in reduced tendency to aggregate. All of these activities are efficiently inhibited by recombinant DcR3. [Mh] Termos MeSH primário: Proteína Ligante Fas/química Proteína Ligante Fas/metabolismo Membro 6b de Receptores do Fator de Necrose Tumoral/química Membro 6b de Receptores do Fator de Necrose Tumoral/metabolismo [Mh] Termos MeSH secundário: Apoptose Sítios de Ligação Sobrevivência Celular/efeitos dos fármacos Cristalografia por Raios X Proteína Ligante Fas/genética Glicosilação Seres Humanos Células Jurkat Modelos Moleculares Mutação Ligação Proteica Conformação Proteica Proteínas Recombinantes/farmacologia Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo Receptor fas/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (FAS protein, human); 0 (FASLG protein, human); 0 (Fas Ligand Protein); 0 (Receptors, Tumor Necrosis Factor, Member 6b); 0 (Recombinant Proteins); 0 (TNFRSF6B protein, human); 0 (TNFSF14 protein, human); 0 (TNFSF15 protein, human); 0 (Tumor Necrosis Factor Ligand Superfamily Member 14); 0 (Tumor Necrosis Factor Ligand Superfamily Member 15); 0 (fas Receptor) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161103 [St] Status: MEDLINE

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[PMID]: 27748813 [Au] Autor: Zhang X; Takata K; Cui W; Miyata-Takata T; Sato Y; Noujima-Harada M; Yoshino T [Ad] Endereço: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700­8558, Japan. [Ti] Título: Protocadherin γ A3 is expressed in follicular lymphoma irrespective of BCL2 status and is associated with tumor cell growth. [So] Source: Mol Med Rep;14(5):4622-4628, 2016 Nov. [Is] ISSN: 1791-3004 [Cp] País de publicação: Greece [La] Idioma: eng [Ab] Resumo: Protocadherin genes (PCDHs) have been suggested to act as tumor suppressor genes in various tumor types. Previous studies have demonstrated the upregulation of certain PCDH­Î³ subfamily genes in nodal and duodenal follicular lymphoma (FL) using gene expression analyses. However, the mechanisms and associated molecular function of PCDH­Î³ subfamily gene upregulation in FL remain to be elucidated. The present study examined the expression of PCDHGA3, an upregulated PCDH­Î³ gene subfamily member, in B­cell lymphoma 2 (BCL2)­positive and ­negative FL, and evaluated its association with tumor cell proliferation in an FL­derived cell line. Immunohistochemical analysis demonstrated that the majority of FL grade 1­2 samples (19/20; 95%) and over half of grade 3A FL samples (5/9; 56%) were PCDHGA3­positive, whereas only 1/17 reactive lymphoid hyperplasia samples was positive. Notably, this positivity was widely observed in samples of BCL2­negative FL (13/15; 87%) and FL with diffuse area (10/10; 100%). The FL­derived cell line FL18 exhibited strong PCDHGA3 expression, similar to the patient samples, and its proliferation was suppressed by PCDHGA3 gene knockdown. Genes expressed concomitantly with PCDHGA3 were selected from gene expression data, and TNFRSF6B, a member of the tumor necrosis factor receptor superfamily, was among the top five most strongly correlated genes. Coexpression of TNFRSF6B and PCDHGA3 was observed immunohistochemically in FL18 cells, suggesting potential cooperation in tumor cell maintenance. In conclusion, the results of the present study indicated that PCDHGA3 was expressed in FL irrespective of BCL2 status and grading and was associated with cell proliferation. Further studies involving molecular genetic analyses are required to elucidate the mechanisms underlying the activity of PCDHGA3 in FL. [Mh] Termos MeSH primário: Biomarcadores Tumorais/biossíntese Caderinas/biossíntese Linfoma Folicular/genética Proteínas Proto-Oncogênicas c-bcl-2/biossíntese Membro 6b de Receptores do Fator de Necrose Tumoral/biossíntese [Mh] Termos MeSH secundário: Biomarcadores Tumorais/genética Caderinas/genética Linhagem Celular Tumoral Proliferação Celular/genética Regulação Neoplásica da Expressão Gênica/genética Seres Humanos Hibridização in Situ Fluorescente Linfoma Folicular/patologia Proteínas Proto-Oncogênicas c-bcl-2/genética Membro 6b de Receptores do Fator de Necrose Tumoral/genética [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Biomarkers, Tumor); 0 (Cadherins); 0 (Gamma-protocadherins); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Receptors, Tumor Necrosis Factor, Member 6b); 0 (TNFRSF6B protein, human) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170417 [Lr] Data última revisão: 170417 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161026 [St] Status: MEDLINE [do] DOI: 10.3892/mmr.2016.5808

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[PMID]: 27595094 [Au] Autor: Bamias G; Gizis M; Delladetsima I; Laoudi E; Siakavellas SI; Koutsounas I; Kaltsa G; Vlachogiannakos J; Vafiadis-Zouboulis I; Daikos GL; Papatheodoridis GV; Ladas SD [Ad] Endereço: Academic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens 11527, Greece. [Ti] Título: Elevated Serum Levels of the Antiapoptotic Protein Decoy-Receptor 3 Are Associated with Advanced Liver Disease. [So] Source: Can J Gastroenterol Hepatol;2016:2637010, 2016. [Is] ISSN: 2291-2797 [Cp] País de publicação: Egypt [La] Idioma: eng [Ab] Resumo: Background. Decoy-receptor 3 (DcR3) exerts antiapoptotic and immunomodulatory function and is overexpressed in neoplastic and inflammatory conditions. Serum DcR3 (sDcR3) levels during the chronic hepatitis/cirrhosis/hepatocellular carcinoma (HCC) sequence have not been explored. Objective. To assess the levels and significance of sDcR3 protein in various stages of chronic liver disease. Methods. We compared sDcR3 levels between healthy controls and patients with chronic viral hepatitis (CVH), decompensated cirrhosis (DC), and HCC. Correlations between sDcR3 levels and various patient- and disease-related factors were analyzed. Results. sDcR3 levels were significantly higher in patients with CVH than in controls (P < 0.01). sDcR3 levels were elevated in DC and HCC, being significantly higher compared not only to controls (P < 0.001 for both) but to CVH patients as well (P < 0.001 for both). In addition, DcR3 protein was detected in large quantities in the ascitic fluid of cirrhotics. In patients with CVH, sDcR3 significantly correlated to fibrosis severity, as estimated by Ishak score (P = 0.019) or by liver stiffness measured with elastography (Spearman r = 0.698, P < 0.001). In cirrhotic patients, significant positive correlations were observed between sDcR3 levels and markers of severity of hepatic impairment, including MELD score (r = 0.653, P < 0.001). Conclusions. Circulating levels of DcR3 are elevated during chronic liver disease and correlate with severity of liver damage. sDcR3 may serve as marker for liver fibrosis severity and progression to end-stage liver disease. [Mh] Termos MeSH primário: Carcinoma Hepatocelular/sangue Hepatite Crônica/sangue Cirrose Hepática/sangue Neoplasias Hepáticas/sangue Membro 6b de Receptores do Fator de Necrose Tumoral/sangue [Mh] Termos MeSH secundário: Adulto Idoso Idoso de 80 Anos ou mais Biomarcadores/sangue Estudos de Casos e Controles Feminino Seres Humanos Masculino Meia-Idade Prognóstico [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Biomarkers); 0 (Receptors, Tumor Necrosis Factor, Member 6b); 0 (TNFRSF6B protein, human) [Em] Mês de entrada: 1703 [Cu] Atualização por classe: 170817 [Lr] Data última revisão: 170817 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160906 [St] Status: MEDLINE [do] DOI: 10.1155/2016/2637010

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[PMID]: 27510663 [Au] Autor: Lin CK; Ting CC; Tsai WC; Chen YW; Hueng DY [Ad] Endereço: Department of Pathology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan, Republic of China. [Ti] Título: A tissue microarray study of toll-like receptor 4, decoy receptor 3, and external signal regulated kinase 1/2 expressions in astrocytoma. [So] Source: Indian J Pathol Microbiol;59(3):294-300, 2016 Jul-Sep. [Is] ISSN: 0974-5130 [Cp] País de publicação: India [La] Idioma: eng [Ab] Resumo: INTRODUCTION: Decoy receptor 3 (DcR3) functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor family. It is highly expressed in many tumors and its expression can be regulated by the MAPK/ERK signaling pathway and ERK is a vital member of this pathway. Toll-like receptor 4 (TLR4) is expressed on immune cells. Increased TLR4 expression has been associated with various types of cancers. MATERIAL AND METHODS: The study was conducted to investigate the expression of DcR3, ERK1/2, and TLR4 in astrocytomas and evaluate if they are validating markers for discriminating glioblastoma from anaplastic astrocytoma in limited surgical specimen. Expression of DcR3, ERK1/2, and TLR4 was determined by immunohistochemical staining of tissue microarray from 48 paraffin-embedded tissues. A binary logistic regression method was used to generate functions that discriminate between anaplastic astrocytomas and glioblastomas. RESULTS: The expression of TLR4 and DcR3 was significantly higher in glioblastomas than in anaplastic astrocytomas. DcR3 could discriminate anaplastic astrocytomas from glioblastomas with high sensitivity (93.8%), specificity (90%), and accuracy (92.3%). CONCLUSION: Our results suggest that DcR3 may be a useful marker for discriminating anaplastic astrocytomas from glioblastomas. [Mh] Termos MeSH primário: Astrocitoma/patologia Análise em Microsséries Proteína Quinase 1 Ativada por Mitógeno/análise Proteína Quinase 3 Ativada por Mitógeno/análise Membro 6b de Receptores do Fator de Necrose Tumoral/análise Receptor 4 Toll-Like/análise [Mh] Termos MeSH secundário: Astrocitoma/diagnóstico Biomarcadores/análise Diagnóstico Diferencial Seres Humanos Imuno-Histoquímica Patologia Clínica/métodos Sensibilidade e Especificidade [Pt] Tipo de publicação: EVALUATION STUDIES; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Biomarkers); 0 (Receptors, Tumor Necrosis Factor, Member 6b); 0 (TLR4 protein, human); 0 (Toll-Like Receptor 4); EC 2.7.11.24 (MAPK1 protein, human); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) [Em] Mês de entrada: 1703 [Cu] Atualização por classe: 170313 [Lr] Data última revisão: 170313 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160812 [St] Status: MEDLINE [do] DOI: 10.4103/0377-4929.188122

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[PMID]: 27316538 [Au] Autor: Chiu CW; Huang WH; Lin SJ; Tsai MJ; Ma H; Hsieh SL; Cheng H [Ad] Endereço: Department and Institute of Pharmacology, National Yang-Ming University, Taipei, 11221, Taiwan. [Ti] Título: The immunomodulator decoy receptor 3 improves locomotor functional recovery after spinal cord injury. [So] Source: J Neuroinflammation;13(1):154, 2016 Jun 17. [Is] ISSN: 1742-2094 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: Spinal cord injury (SCI) causes loss of neurons and axons and results in motor and sensory function impairments. SCI elicits an inflammatory response and induces the infiltration of immune cells, predominantly macrophages, to the injured site. Decoy receptor 3 (DcR3), also known as tumor necrosis factor receptor superfamily member (TNFRSF)-6B, is a pleiotropic immunomodulator capable of inducing macrophage differentiation into the M2 phenotype and enhancing angiogenesis. Because M2 macrophages are crucial for the recovery of impaired motor functions, we ask whether DcR3 is beneficial for the functional recovery of locomotion in Sprague-Dawley (SD) rats after SCI. METHODS: Contusion injury of the spinal cord was performed using a New York University impactor at the ninth thoracic vertebrae, followed by intrathecal injection of 15 µg recombinant protein comprising DcR3 (DcR3.Fc) in 5 µl of normal saline as the treatment, or 5 µl of normal saline as the control, into the injury epicenter. Functional recovery was evaluated using an open-field test weekly up to 6 weeks after injury. The cavity size and myelin sparing in the rostral-to-caudal region, including the epicenter of the injury, were then examined in SCI rats by histological staining. The expression of anti-inflammatory cytokines and the presence of M2 macrophages were determined by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry at 7 day after SCI. Statistical analysis was performed using a two-tailed Student's t test. RESULTS: Intrathecal administration of DcR3.Fc significantly improved locomotor function and reduced secondary injury with a smaller wound cavity and increased myelin sparing at the lesion site. Compared with the control group, DcR3.Fc-treated rats had increased vascularization at the injury epicenter along with higher levels of interleukin (IL)-4 and IL-10 and lower level of IL-1ß on DcR3.Fc-treated rats at day 7 after SCI. Moreover, higher levels of arginase I (Arg I) and CD206 (M2 macrophage markers) and RECA-1 (endothelial marker) were observed in the epicenter on day 7 after SCI by immunofluorescence staining. CONCLUSIONS: These results indicated that DcR3.Fc may promote the M2 macrophage infiltration and enhanced angiogenesis at the lesion site, thus preserving a greater amount of spinal cord tissues and enhancing functional recovery after SCI. [Mh] Termos MeSH primário: Locomoção/fisiologia Membro 6b de Receptores do Fator de Necrose Tumoral/uso terapêutico Recuperação de Função Fisiológica/fisiologia Traumatismos da Medula Espinal/tratamento farmacológico Traumatismos da Medula Espinal/metabolismo [Mh] Termos MeSH secundário: Animais Células Cultivadas Feminino Seres Humanos Locomoção/efeitos dos fármacos Ratos Ratos Sprague-Dawley Membro 6b de Receptores do Fator de Necrose Tumoral/farmacologia Recuperação de Função Fisiológica/efeitos dos fármacos Traumatismos da Medula Espinal/patologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Receptors, Tumor Necrosis Factor, Member 6b); 0 (TNFRSF6B protein, human) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171010 [Lr] Data última revisão: 171010 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160619 [St] Status: MEDLINE [do] DOI: 10.1186/s12974-016-0623-6

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[PMID]: 27251675 [Au] Autor: Maruyama H; Hirayama K; Nagai M; Ebihara I; Shimohata H; Kobayashi M [Ad] Endereço: Department of Nephrology, Tokyo Medical University Ibaraki Medical Center, 3-20-1, Chuo, Ami, Ibaraki, 300-0395, Japan. [Ti] Título: Serum decoy receptor 3 levels are associated with the disease activity of MPO-ANCA-associated renal vasculitis. [So] Source: Clin Rheumatol;35(10):2469-76, 2016 Oct. [Is] ISSN: 1434-9949 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: Type 17 T-helper (Th17) cells have been suggested to be involved in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Th17 cell proliferation is promoted by tumor necrosis factor (TNF)-like ligand 1A (TL1A), which binds to death receptor 3 (DR3) expressed on Th17 cells. Decoy receptor 3 (DcR3) is known to block the TL1A-DR3 pathway by binding TL1A. To evaluate the Th17-TL1A systems as disease activity markers in AAV, we investigated the serum levels of TL1A and DcR3 in AAV patients. Serum IL-17, IL-23, TL1A, and DcR3 were measured by ELISA in 24 AAV patients with microscopic polyangiitis before the initial treatment, 24 AAV patients during remission, and 20 control subjects. There were no significant differences in serum IL-17, IL-23, and TL1A levels among the active-vasculitis patients, inactive-vasculitis patients, and controls. The mean serum DcR3 level was significantly higher in the active-vasculitis patients than in the inactive-vasculitis patients and controls (P < 0.0001, respectively). There were significant positive correlations between the serum DcR3 levels and Birmingham Vasculitis Activity Score (BVAS), myeloperoxidase (MPO)-ANCA titers, white blood cell counts, serum creatinine levels, and serum C-reactive protein levels. In a multiple regression analysis, there was a significant positive correlation between the serum DcR3 level and BVAS (ß = 0.650, P = 0.0462). The mean BVAS level was significantly higher in the active-vasculitis patients with high serum DcR3 levels than in those with the low serum DcR3 levels (P = 0.0202). The serum level of DcR3 may be a useful marker for disease activity in AAV. [Mh] Termos MeSH primário: Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue Nefropatias/sangue Membro 6b de Receptores do Fator de Necrose Tumoral/sangue [Mh] Termos MeSH secundário: Idoso Idoso de 80 Anos ou mais Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico Anticorpos Anticitoplasma de Neutrófilos/sangue Biomarcadores/sangue Feminino Seres Humanos Interleucina-17/sangue Interleucina-23/sangue Nefropatias/diagnóstico Masculino Meia-Idade Índice de Gravidade de Doença Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies, Antineutrophil Cytoplasmic); 0 (Biomarkers); 0 (Interleukin-17); 0 (Interleukin-23); 0 (Receptors, Tumor Necrosis Factor, Member 6b); 0 (TNFSF15 protein, human); 0 (Tumor Necrosis Factor Ligand Superfamily Member 15) [Em] Mês de entrada: 1702 [Cu] Atualização por classe: 171013 [Lr] Data última revisão: 171013 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160603 [St] Status: MEDLINE [do] DOI: 10.1007/s10067-016-3321-y

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