Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy.
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2012 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/8077 |
Resumo: | Rega Institute for Medical Research. K. U. Leuven. Leuven, Belgium |
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Moens, BrittaDecanine, DanieleMenezes, Soraya MariaCunha, Antonio Ricardo KhouriSantos, Gilvanéia SilvaLópez, GiovanniAlvarez, CarolinaTalledo, MichaelGotuzzo, EduardoKruschewsky, Ramon de AlmeidaCastro Filho, Bernardo GalvãoVandamme, Anne-MiekeVan Weyenbergh, Johan Jozef Rosa Maria2014-07-24T18:48:33Z2014-07-24T18:48:33Z2012MOENS, B. Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. PLoS Neglected Tropical Diseasesa, v. 6, n. 7, p. e1729, 2012.1935-2735https://www.arca.fiocruz.br/handle/icict/807710.1371/journal.pntd.0001729engPublic Library of ScienceAscorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleRega Institute for Medical Research. K. U. Leuven. Leuven, BelgiumFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilRega Institute for Medical Research K. U. Leuven. Leuven, BelgiumRega Institute for Medical Research. K. U. Leuven. Leuven, Belgium / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilInstituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia, Lima, PeruRega Institute for Medical Research. K. U. Leuven. Leuven, Belgium / Instituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia, Lima, PeruInstituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia, Lima, PeruInstituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia, Lima, Peru / Universidad Peruana Cayetano Heredia. Departamento de Medicina, Facultad de Medicina. Lima, PeruBahia School of Medicine and Public Health. Salvador-BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Bahia School of Medicine and Public Health. Salvador-BA, BrasilRega Institute for Medical Research. K. U. Leuven. Leuven, Belgium / Universidade Nova de Lisboa. Instituto de Higiene e Medicina Tropical. Centro de Malária e outras Doenças Tropicais. Lisboa, PortugalRega Institute for Medical Research. K. U. Leuven. Leuven, Belgium / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilBACKGROUND: Clear therapeutic guidelines for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are missing due to the lack of randomized double-blind controlled clinical trials. Moderate yet similar clinical benefit has been demonstrated for IFN-α and high-dose ascorbic acid (AA) monotherapy in a large open clinical trial. However, there is a lack of in vivo and in vitro studies exploring and comparing the effects of high-dose AA and IFN-α treatment in the context of HAM/TSP. Therefore, we performed the first comparative analysis of the ex vivo and in vitro molecular and cellular mechanisms of action of IFN-α and high-dose AA in HAM/TSP. PRINCIPAL FINDINGS: Through thymidine incorporation and quantification of Th1/Th2/Th17 cytokines, we demonstrate that high-dose AA displays differential and superior antiproliferative and immunomodulatory effects over IFN-α in HAM/TSP PBMCs ex vivo. In addition, high-dose AA, but not IFN-α, induced cell death in both HAM/TSP PBMCs and HTLV-1-infected T-cell lines MT-2 and MT-4. Microarray data combined with pathway analysis of MT-2 cells revealed AA-induced regulation of genes associated with cell death, including miR-155. Since miR-155 has recently been demonstrated to up-regulate IFN-γ, this microRNA might represent a novel therapeutic target in HAM/TSP, as recently demonstrated in multiple sclerosis, another neuroinflammatory disease. On the other hand, IFN-α selectively up-regulated antiviral and immune-related genes. CONCLUSIONS: In comparison to IFN-α, high-dose AA treatment has superior ex vivo and in vitro cell death-inducing, antiproliferative and immunomodulatory anti-HTLV-1 effects. Differential pathway activation by both drugs opens up avenues for targeted treatment in specific patient subsets.Antineoplásicos/farmacologiaÁcido Ascórbico/farmacologiaMorte Celular/efeitos de drogasFatores Imunológicos/farmacologiaLeucemia-Linfoma de Células T do Adulto/quimioterapiaAdultoIdosoCélulas CultivadasFemininoPerfilação da Expressão GênicaHumanosInterferon-alfa/farmacologiaMasculinoAnálise em MicrossériesMeia-IdadeTécnicas de Cultura de ÓrgãosDoenças da Medula Espinal/quimioterapiaAdulto Joveminfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALMoens, B Ascorbic Acid....pdfMoens, B Ascorbic Acid....pdfapplication/pdf730046https://www.arca.fiocruz.br/bitstream/icict/8077/1/Moens%2c%20B%20Ascorbic%20Acid....pdf97e66f8a63252afb3abb035fbba7cc97MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/8077/2/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD52TEXTMoens, B Ascorbic Acid....pdf.txtMoens, B Ascorbic Acid....pdf.txtExtracted texttext/plain66108https://www.arca.fiocruz.br/bitstream/icict/8077/3/Moens%2c%20B%20Ascorbic%20Acid....pdf.txtd235fafdbaf0f63d40471f7495dc0aa5MD53icict/80772023-03-15 14:33:24.61oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:33:24Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. |
| title |
Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. |
| spellingShingle |
Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. Moens, Britta Antineoplásicos/farmacologia Ácido Ascórbico/farmacologia Morte Celular/efeitos de drogas Fatores Imunológicos/farmacologia Leucemia-Linfoma de Células T do Adulto/quimioterapia Adulto Idoso Células Cultivadas Feminino Perfilação da Expressão Gênica Humanos Interferon-alfa/farmacologia Masculino Análise em Microsséries Meia-Idade Técnicas de Cultura de Órgãos Doenças da Medula Espinal/quimioterapia Adulto Jovem |
| title_short |
Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. |
| title_full |
Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. |
| title_fullStr |
Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. |
| title_full_unstemmed |
Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. |
| title_sort |
Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. |
| author |
Moens, Britta |
| author_facet |
Moens, Britta Decanine, Daniele Menezes, Soraya Maria Cunha, Antonio Ricardo Khouri Santos, Gilvanéia Silva López, Giovanni Alvarez, Carolina Talledo, Michael Gotuzzo, Eduardo Kruschewsky, Ramon de Almeida Castro Filho, Bernardo Galvão Vandamme, Anne-Mieke Van Weyenbergh, Johan Jozef Rosa Maria |
| author_role |
author |
| author2 |
Decanine, Daniele Menezes, Soraya Maria Cunha, Antonio Ricardo Khouri Santos, Gilvanéia Silva López, Giovanni Alvarez, Carolina Talledo, Michael Gotuzzo, Eduardo Kruschewsky, Ramon de Almeida Castro Filho, Bernardo Galvão Vandamme, Anne-Mieke Van Weyenbergh, Johan Jozef Rosa Maria |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Moens, Britta Decanine, Daniele Menezes, Soraya Maria Cunha, Antonio Ricardo Khouri Santos, Gilvanéia Silva López, Giovanni Alvarez, Carolina Talledo, Michael Gotuzzo, Eduardo Kruschewsky, Ramon de Almeida Castro Filho, Bernardo Galvão Vandamme, Anne-Mieke Van Weyenbergh, Johan Jozef Rosa Maria |
| dc.subject.decs.pt_BR.fl_str_mv |
Antineoplásicos/farmacologia Ácido Ascórbico/farmacologia Morte Celular/efeitos de drogas Fatores Imunológicos/farmacologia Leucemia-Linfoma de Células T do Adulto/quimioterapia Adulto Idoso Células Cultivadas Feminino Perfilação da Expressão Gênica Humanos Interferon-alfa/farmacologia Masculino Análise em Microsséries Meia-Idade Técnicas de Cultura de Órgãos Doenças da Medula Espinal/quimioterapia Adulto Jovem |
| topic |
Antineoplásicos/farmacologia Ácido Ascórbico/farmacologia Morte Celular/efeitos de drogas Fatores Imunológicos/farmacologia Leucemia-Linfoma de Células T do Adulto/quimioterapia Adulto Idoso Células Cultivadas Feminino Perfilação da Expressão Gênica Humanos Interferon-alfa/farmacologia Masculino Análise em Microsséries Meia-Idade Técnicas de Cultura de Órgãos Doenças da Medula Espinal/quimioterapia Adulto Jovem |
| description |
Rega Institute for Medical Research. K. U. Leuven. Leuven, Belgium |
| publishDate |
2012 |
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2012 |
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2014-07-24T18:48:33Z |
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2014-07-24T18:48:33Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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MOENS, B. Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. PLoS Neglected Tropical Diseasesa, v. 6, n. 7, p. e1729, 2012. |
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https://www.arca.fiocruz.br/handle/icict/8077 |
| dc.identifier.issn.none.fl_str_mv |
1935-2735 |
| dc.identifier.doi.none.fl_str_mv |
10.1371/journal.pntd.0001729 |
| identifier_str_mv |
MOENS, B. Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. PLoS Neglected Tropical Diseasesa, v. 6, n. 7, p. e1729, 2012. 1935-2735 10.1371/journal.pntd.0001729 |
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Public Library of Science |
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