Author | Moens, Britta | |
Author | Decanine, Daniele | |
Author | Menezes, Soraya Maria | |
Author | Cunha, Antonio Ricardo Khouri | |
Author | Santos, Gilvanéia Silva | |
Author | López, Giovanni | |
Author | Alvarez, Carolina | |
Author | Talledo, Michael | |
Author | Gotuzzo, Eduardo | |
Author | Kruschewsky, Ramon de Almeida | |
Author | Castro Filho, Bernardo Galvão | |
Author | Vandamme, Anne-Mieke | |
Author | Van Weyenbergh, Johan Jozef Rosa Maria | |
Access date | 2014-07-24T18:48:33Z | |
Available date | 2014-07-24T18:48:33Z | |
Document date | 2012 | |
Citation | 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. | pt_BR |
ISSN | 1935-2735 | |
URI | https://www.arca.fiocruz.br/handle/icict/8077 | |
Language | eng | pt_BR |
Publisher | Public Library of Science | pt_BR |
Rights | open access | pt_BR |
Title | Ascorbic acid has superior ex vivo antiproliferative, cell death-inducing and immunomodulatory effects over IFN-α in HTLV-1-associated myelopathy. | pt_BR |
Type | Article | pt_BR |
DOI | 10.1371/journal.pntd.0001729 | |
Abstract | BACKGROUND: 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. | pt_BR |
Affilliation | Rega Institute for Medical Research. K. U. Leuven. Leuven, Belgium | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Rega Institute for Medical Research K. U. Leuven. Leuven, Belgium | pt_BR |
Affilliation | Rega Institute for Medical Research. K. U. Leuven. Leuven, Belgium / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Instituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia, Lima, Peru | pt_BR |
Affilliation | Rega Institute for Medical Research. K. U. Leuven. Leuven, Belgium / Instituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia, Lima, Peru | pt_BR |
Affilliation | Instituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia, Lima, Peru | pt_BR |
Affilliation | Instituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia, Lima, Peru / Universidad Peruana Cayetano Heredia. Departamento de Medicina, Facultad de Medicina. Lima, Peru | pt_BR |
Affilliation | Bahia School of Medicine and Public Health. Salvador-BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Bahia School of Medicine and Public Health. Salvador-BA, Brasil | pt_BR |
Affilliation | Rega 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, Portugal | pt_BR |
Affilliation | Rega Institute for Medical Research. K. U. Leuven. Leuven, Belgium / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
DeCS | Antineoplásicos/farmacologia | pt_BR |
DeCS | Ácido Ascórbico/farmacologia | pt_BR |
DeCS | Morte Celular/efeitos de drogas | pt_BR |
DeCS | Fatores Imunológicos/farmacologia | pt_BR |
DeCS | Leucemia-Linfoma de Células T do Adulto/quimioterapia | pt_BR |
DeCS | Adulto | pt_BR |
DeCS | Idoso | pt_BR |
DeCS | Células Cultivadas | pt_BR |
DeCS | Feminino | pt_BR |
DeCS | Perfilação da Expressão Gênica | pt_BR |
DeCS | Humanos | pt_BR |
DeCS | Interferon-alfa/farmacologia | pt_BR |
DeCS | Masculino | pt_BR |
DeCS | Análise em Microsséries | pt_BR |
DeCS | Meia-Idade | pt_BR |
DeCS | Técnicas de Cultura de Órgãos | pt_BR |
DeCS | Doenças da Medula Espinal/quimioterapia | pt_BR |
DeCS | Adulto Jovem | pt_BR |