EDECIO CUNHA NETO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/60 - Laboratório de Imunologia Clínica e Alergia, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/60 - Laboratório de Imunologia Clínica e Alergia, Hospital das Clínicas, Faculdade de Medicina - Líder
9 resultados
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- Integrative analysis of microRNA and mRNA expression profiles of monocyte-derived dendritic cells differentiation during experimental cerebral malaria(2020) APARECIDA, Patricia; DURSO, Danielle Fernandes; CAVALCANTE, Fernanda Chacon; ZANIRATTO, Ricardo; CARVALHO-SILVA, Ana Carolina; CUNHA-NETO, Edecio; GOLENBOCK, Douglas Taylor; FERREIRA, Ludmila Rodrigues Pinto; GAZZINELLI, Ricardo TostesHeterogeneity and high plasticity are common features of cells from the mononuclear phagocyte system: monocytes (MOs), macrophages, and dendritic cells (DCs). Upon activation by microbial agents, MO can differentiate into MO-derived DCs (MODCs). In previous work, we have shown that during acute infection with Plasmodium berghei ANKA (PbA), MODCs become, transiently, the main CD11b(+) myeloid population in the spleen (SP) and once recruited to the brain play an important role in the development of experimental cerebral malaria (ECM). Here, we isolated 4 cell populations: bone marrow (BM) MOs (BM-MOs) and SP-MOs from uninfected mice; BM inflammatory MOs (BM-iMOs) and SP-MODCs from PbA-infected mice and used a system biology approach to a holistic transcriptomic comparison and provide an interactome analysis by integrating differentially expressed miRNAs (DEMs) and their differentially expressed gene targets (DEGs) data. The Jaccard index (JI) was used for gauging the similarity and diversity among these cell populations. Whereas BM-MOs, BM-iMOs, and SP-MOs presented high similarity of DEGs, SP-MODCs distinguished by showing a greater number of DEGs. Moreover, functional analysis identified an enrichment in canonical pathways, such as DC maturation, neuroinflammation, and IFN signaling. Upstream regulator analysis identified IFN gamma as the potential upstream molecule that can explain the observed DEMs-Target DEGs intersections in SP-MODCs. Finally, directed target analysis and in vivo/ex vivo assays indicate that SP-MODCs differentiate in the SP and IFN gamma is a main driver of this process.
- miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy(2020) LAUGIER, Laurie; FERREIRA, Ludmila Rodrigues Pinto; FERREIRA, Frederico Moraes; CABANTOUS, Sandrine; FRADE, Amanda Farage; NUNES, Joao Paulo; RIBEIRO, Rafael Almeida; BROCHET, Pauline; TEIXEIRA, Priscila Camillo; SANTOS, Ronaldo Honorato Barros; BOCCHI, Edimar A.; BACAL, Fernando; CANDIDO, Darlan da Silva; MASO, Vanessa Escolano; NAKAYA, Helder I.; KALIL, Jorge; CUNHA-NETO, Edecio; CHEVILLARD, ChristopheChronic Chagas disease cardiomyopathy (CCC), an especially aggressive inflammatory dilated cardiomyopathy caused by lifelong infection with the protozoan Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Although chronic myocarditis may play a major pathogenetic role, little is known about the molecular mechanisms responsible for its severity. The aim of this study is to study the genes and microRNAs expression in tissues and their connections in regards to the pathobiological processes. To do so, we integrated for the first time global microRNA and mRNA expression profiling from myocardial tissue of CCC patients employing pathways and network analyses. We observed an enrichment in biological processes and pathways associated with the immune response and metabolism. IFN gamma, TNF and NFkB were the top upstream regulators. The intersections between differentially expressed microRNAs and differentially expressed target mRNAs showed an enrichment in biological processes such as Inflammation, inflammation, Th1/IFN-gamma-inducible genes, fibrosis, hypertrophy, and mitochondrial/oxidative stress/antioxidant response. MicroRNAs also played a role in the regulation of gene expression involved in the key cardiomyopathy-related processes fibrosis, hypertrophy, myocarditis and arrhythmia. Significantly, a discrete number of differentially expressed microRNAs targeted a high number of differentially expressed mRNAs (>20) in multiple processes. Our results suggest that miRNAs orchestrate expression of multiple genes in the major pathophysiological processes in CCC heart tissue. This may have a bearing on pathogenesis, biomarkers and therapy. Author summary Chronic Chagas disease cardiomyopathy (CCC), an aggressive dilated cardiomyopathy caused by Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Little is known about the molecular mechanisms responsible for its severity. Authors study the possible role of microRNAs in the regulation of gene expression in relevant pathways and pathobiological processes. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) -small RNAs that can regulate gene expression-associated to severe cardiomyopathy development. The inflammatory mediator Interferon-gamma was the most likely inducer of gene expression in CCC, and most genes belonged to the immune response, fibrosis, hypertrophy and mitochondrial metabolism. A discrete number of differentially expressed mRNAs targeted a high number of differentially expressed mRNAs in multiple processes. Moreover, several pathways had multiple targets regulated by microRNAs, suggesting synergic effect. Results suggest that microRNAs orchestrate expression of multiple genes in the major pathophysiological processes in CCC heart tissue.
conferenceObject Prolonged use of pentoxifylline prevents progression of myocardial perfusion disturbance and reduces inflammation in the hamster experimental model of chronic Chagas cardiomyopathy(2020) TANAKA, D. M.; FABRICIO, C. G.; MARIN-NETO, J. A.; BARROS-FILHO, A. C. L.; DELARISSE, M. L.; LOPES, C. D.; OLIVEIRA, L. F. L.; RESENDE, A. R.; MOREIRA, H. T.; MEJIA, J.; HIGUCHI, M. L.; CUNHA-NETO, E.; ROMANO, M. M.; SCHMIDT, A.; SIMOES, M. V.- Circulating plasma microRNAs dysregulation and metabolic endotoxemia induced by a high-fat high-saturated diet(2020) QUINTANILHA, Bruna Jardim; FERREIRA, Ludmila Rodrigues Pinto; FERREIRA, Frederico Moraes; NETO, Edecio Cunha; SAMPAIO, Geni Rodrigues; ROGERO, Marcelo MacedoHigh-fat diet increase two to three times the plasma lipopolysaccharide (LPS) levels and induce subclinical inflammation. Diet can modify gene expression due to epigenetic processes related to MicroRNAs (miRNAs). MicroRNAs (miRNAs) play important role in the post-transcriptional mechanisms involved in regulation of expression of genes related to the inflammatory response. Also, diet can indirectly induce post-transcriptional regulation of gene expression by miRNAs, which may affect the risk for the development of chronic diseases. Objective: This study investigated the effect of high-fat high-saturated meal ingestion on plasma miRNA expression and LPS levels during the postprandial period in healthy women. Methods: An interventional study was carried out in which a high-fat breakfast (1067.45 kcal), composed mainly of saturated fatty acids (56 g), and 500 mL of water, was offered. Blood samples were collected at baseline and 1, 3 and 5 h after meal intake. The studied population consisted of healthy women (n = 11), aged between 20 and 40 years, and body mass index (BMI) between 18.5 and 25 kg/m(2). Plasma levels of lipid profile, cytokines, adhesion molecules, and LPS were measured at the 3 time points. A profile of 752 human plasma miRNA expression was analyzed by real-time PCR assay. These analyzes were performed for all blood collection time-points. Results: Expression profile analysis revealed 33 differentially expressed plasma circulating miRNAs compared to that of the control group. MiR-145-5p and miR-200 were differentially modulated in all time-points post meal consumption. In addition, there was a significant increase in plasma LPS, triglycerides, myristic and palmitic saturated fatty acids levels at the 3 time-points in comparison with the control basal levels. We also observed increased levels of the plasma tumor necrosis factor alpha (TNF-alpha) cytokine and the vascular cell adhesion molecule 1 (VCAM-1) levels after 5 h post meal ingestion. Conclusion: Ingestion of high-fat high-saturated meal was able to induce metabolic endotoxemia and increase the expression of pro-inflammatory molecules such as TNF-alpha and VCAM-1, as well as modulating circulating miRNAs possibly controlling inflammatory and lipid metabolism proteins at the postprandial period.
- Blood Gene Signatures of Chagas Cardiomyopathy With or Without Ventricular Dysfunction (vol 215, pg 387, 2017)(2020) FERREIRA, Ludmila Rodrigues Pinto; FERREIRA, Frederico Moraes; NAKAYA, Helder Imoto; DENG, Xutao; CANDIDO, Darlan da Silva; OLIVEIRA, Lea Campos de; BILLAUD, Jean-Noel; LANTERI, Marion C.; RIGAUD, Vagner Oliveira-Carvalho; SEIELSTAD, Mark; KALIL, Jorge; FERNANDES, Fabio; RIBEIRO, Antonio Luiz Pinho; SABINO, Ester Cerdeira; CUNHA-NETO, Edecio
- Polymorphisms in Genes Affecting Interferon-gamma Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy(2020) FRADE-BARROS, Amanda Farage; IANNI, Barbara Maria; CABANTOUS, Sandrine; PISSETTI, Cristina Wide; SABA, Bruno; LIN-WANG, Hui Tzu; BUCK, Paula; MARIN-NETO, Jose Antonio; SCHMIDT, Andre; DIAS, Fabricio; HIRATA, Mario Hiroyuki; SAMPAIO, Marcelo; FRAGATA, Abilio; PEREIRA, Alexandre Costa; DONADI, Eduardo; RODRIGUES, Virmondes; KALIL, Jorge; CHEVILLARD, Christophe; CUNHA-NETO, EdecioBackground:Chagas disease, caused by the protozoanTrypanosoma cruzi, is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is the most important clinical consequence ofT. cruziinfection, while the others remain asymptomatic (ASY). IFN-gamma and IFN-gamma-producing Th1-type T cells are increased in peripheral blood and CCC myocardium as compared to ASY patients, while the Th1-antagonizing cytokine IL-10 is more expressed in ASY patients. Importantly IFN-gamma-producing Th1-type T cells are the most frequent cytokine-producing T cell subset in CCC myocardium, while expression of Th1-antagonizing cytokines IL-10 and IL-4 is unaltered. The control of IFN-gamma production by Th1-type T cells may be a key event for progression toward CCC. A genetic component to disease progression was suggested by the familial aggregation of cases and the association of gene polymorphisms with CCC development. We here investigate the role of gene polymorphisms (SNPs) in several genes involved in the control of IFN-gamma production and Th1 T cell differentiation in CCC development. Methods:We studied a Brazilian population including 315 CCC cases and 118 ASY subjects. We assessed 35 Tag SNPs designed to represent all the genetic information contained in theIL12B, IL10, IFNG, andIL4genes. Results:We found 2IL12SNPs (rs2546893, rs919766) and a trend of association for aIL10SNP (rs3024496) to be significantly associated with the ASY group. these associations were confirmed by multivariate analysis and allele tests. The rs919766C, 12rs2546893G, and rs3024496C alleles were associated to an increase risk to CCC development. Conclusions:Our data show that novel polymorphisms affectingIL12BandIL10, but notIFNGorIL4genes play a role in genetic susceptibility to CCC development. This might indicate that the increased Th1 differentiation and IFN-gamma production associated with CCC is genetically controlled.
- Polymorphisms in Genes Affecting Interferon-gamma Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy (vol 11, 1386, 2020)(2020) FRADE-BARROS, Amanda Farage; IANNI, Barbara Maria; CABANTOUS, Sandrine; PISSETTI, Cristina Wide; SABA, Bruno; LIN-WANG, Hui Tzu; BUCK, Paula; MARIN-NETO, Jose Antonio; SCHMIDT, Andre; DIAS, Fabricio; HIRATA, Mario Hiroyuki; SAMPAIO, Marcelo; FRAGATA, Abilio; PEREIRA, Alexandre Costa; DONADI, Eduardo; RODRIGUES, Virmondes; KALIL, Jorge; CHEVILLARD, Christophe; CUNHA-NETO, Edecio
conferenceObject PROTEIN-PROTEIN INTERACTION NETWORK IN SEPTIC PATIENTS FROM MICROARRAY DATASETS(2020) LEITE, Giuseppe F.; SCICLUNA, Brendon P.; CUNHA-NETO, Edecio; POLL, Tom van der; SALOMAO, Reinaldo- An effective CTL peptide vaccine for Ebola Zaire Based on Survivors' CD8+targeting of a particular nucleocapsid protein epitope with potential implications for COVID-19 vaccine design(2020) V, C. Herst; BURKHOLZ, S.; SIDNEY, J.; SETTE, A.; HARRIS, P. E.; MASSEY, S.; BRASEL, T.; CUNHA-NETO, E.; ROSA, D. S.; CHAO, W. C. H.; CARBACK, R.; HODGE, T.; WANG, L.; CIOTLOS, S.; LLOYD, P.; RUBSAMEN, R.The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple Class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus. (C) 2020 The Author(s).