Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2017 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| DOI: | 10.1038/s41598-017-06275-z |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/20646 |
Resumo: | National Council for Scientific and Technological Development (CNPq) and Bahia Research Foundation (FAPESB). |
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Vasconcelos, Juliana FragaMeira, Cássio SantanaSilva, Daniela NascimentoNonaka, Carolina Kymie VasquesDaltro, Pâmela SantanaMacambira, Simone GarciaDomizi, Pablo DanielBorges, Valéria MatosSantos, Ricardo Ribeiro dosSouza, Bruno Solano de FreitasSoares, Milena Botelho Pereira2017-08-16T17:37:49Z2017-08-16T17:37:49Z2017VASCONCELOS, J. F. et al. Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy. Scientific Reports, v.7, n. 1, p.6171, 2017.2045-2322https://www.arca.fiocruz.br/handle/icict/2064610.1038/s41598-017-06275-zNational Council for Scientific and Technological Development (CNPq) and Bahia Research Foundation (FAPESB).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Universidade Salvador. Escola de Ciências da Saúde. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Universidade Federal de Bahia. Instituto de Ciências da Saúde. Departamento de Bioquímica e Biofísica. Salvador, BA, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Centro de Ciências da Saúde. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilChagas disease cardiomyopathy is a parasite-driven inflammatory disease to which there are no effective treatments. Here we evaluated the therapeutic potential of N,N-dimethylsphingosine(DMS), which blocks the production of sphingosine-1-phosphate(S1P), a mediator of cellular events during inflammatory responses, in a model of chronic Chagas disease cardiomyopathy. DMS-treated, Trypanosoma cruzi-infected mice had a marked reduction of cardiac inflammation, fibrosis and galectin-3 expression when compared to controls. Serum concentrations of galectin-3, IFNγ and TNFα, as well as cardiac gene expression of inflammatory mediators were reduced after DMS treatment. The gene expression of M1 marker, iNOS, was decreased, while the M2 marker, arginase1, was increased. DMS-treated mice showed an improvement in exercise capacity. Moreover, DMS caused a reduction in parasite load in vivo. DMS inhibited the activation of lymphocytes, and reduced cytokines and NO production in activated macrophage cultures in vitro, while increasing IL-1β production. Analysis by qRT-PCR array showed that DMS treatment modulated inflammasome activation induced by T. cruzi on macrophages. Altogether, our results demonstrate that DMS, through anti-parasitic and immunomodulatory actions, can be beneficial in the treatment of chronic phase of T. cruzi infection and suggest that S1P-activated processes as possible therapeutic targets for the treatment of Chagas disease cardiomyopathy.engNature Publishing GroupCardiomiopatia chagásicaDoença de ChagasDoença inflamatóriaTrypanosoma cruziTratamentoRatosChagasic CardiomyopathyChagas diseaseInflammatory diseaseTrypanosoma cruziTreatmentMiceTherapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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| dc.title.pt_BR.fl_str_mv |
Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy |
| title |
Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy |
| spellingShingle |
Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy Vasconcelos, Juliana Fraga Cardiomiopatia chagásica Doença de Chagas Doença inflamatória Trypanosoma cruzi Tratamento Ratos Chagasic Cardiomyopathy Chagas disease Inflammatory disease Trypanosoma cruzi Treatment Mice |
| title_short |
Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy |
| title_full |
Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy |
| title_fullStr |
Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy |
| title_full_unstemmed |
Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy |
| title_sort |
Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy |
| author |
Vasconcelos, Juliana Fraga |
| author_facet |
Vasconcelos, Juliana Fraga Meira, Cássio Santana Silva, Daniela Nascimento Nonaka, Carolina Kymie Vasques Daltro, Pâmela Santana Macambira, Simone Garcia Domizi, Pablo Daniel Borges, Valéria Matos Santos, Ricardo Ribeiro dos Souza, Bruno Solano de Freitas Soares, Milena Botelho Pereira |
| author_role |
author |
| author2 |
Meira, Cássio Santana Silva, Daniela Nascimento Nonaka, Carolina Kymie Vasques Daltro, Pâmela Santana Macambira, Simone Garcia Domizi, Pablo Daniel Borges, Valéria Matos Santos, Ricardo Ribeiro dos Souza, Bruno Solano de Freitas Soares, Milena Botelho Pereira |
| author2_role |
author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Vasconcelos, Juliana Fraga Meira, Cássio Santana Silva, Daniela Nascimento Nonaka, Carolina Kymie Vasques Daltro, Pâmela Santana Macambira, Simone Garcia Domizi, Pablo Daniel Borges, Valéria Matos Santos, Ricardo Ribeiro dos Souza, Bruno Solano de Freitas Soares, Milena Botelho Pereira |
| dc.subject.other.pt_BR.fl_str_mv |
Cardiomiopatia chagásica Doença de Chagas Doença inflamatória Trypanosoma cruzi Tratamento Ratos |
| topic |
Cardiomiopatia chagásica Doença de Chagas Doença inflamatória Trypanosoma cruzi Tratamento Ratos Chagasic Cardiomyopathy Chagas disease Inflammatory disease Trypanosoma cruzi Treatment Mice |
| dc.subject.en.pt_BR.fl_str_mv |
Chagasic Cardiomyopathy Chagas disease Inflammatory disease Trypanosoma cruzi Treatment Mice |
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National Council for Scientific and Technological Development (CNPq) and Bahia Research Foundation (FAPESB). |
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2017 |
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2017-08-16T17:37:49Z |
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2017-08-16T17:37:49Z |
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2017 |
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VASCONCELOS, J. F. et al. Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy. Scientific Reports, v.7, n. 1, p.6171, 2017. |
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https://www.arca.fiocruz.br/handle/icict/20646 |
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2045-2322 |
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10.1038/s41598-017-06275-z |
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VASCONCELOS, J. F. et al. Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy. Scientific Reports, v.7, n. 1, p.6171, 2017. 2045-2322 10.1038/s41598-017-06275-z |
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