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 UFBA |
| Texto Completo: | http://repositorio.ufba.br/ri/handle/ri/15680 |
Resumo: | p. 1-15 |
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Moens, BrittaDecanine, DanieleMenezes, Soraya MariaCunha, Antônio Ricardo KhouriSantos, Gilvanéia SilvaLopez, GiovanniAlvarez, CarolinaTalledo, MichaelGotuzzo, EduardoKruschewsky, Ramon de AlmeidaCastro, Bernardo GalvãoVandamme, Anne MiekeWeyenbergh, Johan VanMoens, BrittaDecanine, DanieleMenezes, Soraya MariaCunha, Antônio Ricardo KhouriSantos, Gilvanéia SilvaLopez, GiovanniAlvarez, CarolinaTalledo, MichaelGotuzzo, EduardoKruschewsky, Ramon de AlmeidaCastro, Bernardo GalvãoVandamme, Anne MiekeWeyenbergh, Johan Van2014-08-22T14:38:43Z2014-08-22T14:38:43Z2012-071549-1277http://repositorio.ufba.br/ri/handle/ri/15680v. 6, n. 7p. 1-15Background 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.Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-08-19T14:50:24Z No. of bitstreams: 1 Ricardo Khouri.pdf: 730046 bytes, checksum: 97e66f8a63252afb3abb035fbba7cc97 (MD5)Approved for entry into archive by Delba Rosa (delba@ufba.br) on 2014-08-22T14:38:43Z (GMT) No. of bitstreams: 1 Ricardo Khouri.pdf: 730046 bytes, checksum: 97e66f8a63252afb3abb035fbba7cc97 (MD5)Made available in DSpace on 2014-08-22T14:38:43Z (GMT). No. of bitstreams: 1 Ricardo Khouri.pdf: 730046 bytes, checksum: 97e66f8a63252afb3abb035fbba7cc97 (MD5) Previous issue date: 2012-07http://dx.doi.org/10.1371/journal.pntd.0001729reponame:Repositório Institucional da UFBAinstname:Universidade Federal da Bahia (UFBA)instacron:UFBAAscorbic Acid Has Superior Ex Vivo Antiproliferative, Cell Death-Inducing and Immunomodulatory Effects over IFN-α in HTLV-1-Associated MyelopathyPLoS Medicineinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessengLICENSElicense.txtlicense.txttext/plain1345https://repositorio.ufba.br/bitstream/ri/15680/2/license.txtff6eaa8b858ea317fded99f125f5fcd0MD52ORIGINALRicardo Khouri.pdfRicardo Khouri.pdfapplication/pdf730046https://repositorio.ufba.br/bitstream/ri/15680/1/Ricardo%20Khouri.pdf97e66f8a63252afb3abb035fbba7cc97MD51TEXTRicardo Khouri.pdf.txtRicardo Khouri.pdf.txtExtracted texttext/plain66106https://repositorio.ufba.br/bitstream/ri/15680/3/Ricardo%20Khouri.pdf.txt3a0320b404fd8944d637350970d558e2MD53ri/156802022-08-08 13:19:12.892oai:repositorio.ufba.br:ri/15680VGVybW8gZGUgTGljZW7vv71hLCBu77+9byBleGNsdXNpdm8sIHBhcmEgbyBkZXDvv71zaXRvIG5vIFJlcG9zaXTvv71yaW8gSW5zdGl0dWNpb25hbCBkYSBVRkJBLgoKIFBlbG8gcHJvY2Vzc28gZGUgc3VibWlzc++/vW8gZGUgZG9jdW1lbnRvcywgbyBhdXRvciBvdSBzZXUgcmVwcmVzZW50YW50ZSBsZWdhbCwgYW8gYWNlaXRhciAKZXNzZSB0ZXJtbyBkZSBsaWNlbu+/vWEsIGNvbmNlZGUgYW8gUmVwb3NpdO+/vXJpbyBJbnN0aXR1Y2lvbmFsIGRhIFVuaXZlcnNpZGFkZSBGZWRlcmFsIGRhIEJhaGlhIApvIGRpcmVpdG8gZGUgbWFudGVyIHVtYSBj77+9cGlhIGVtIHNldSByZXBvc2l077+9cmlvIGNvbSBhIGZpbmFsaWRhZGUsIHByaW1laXJhLCBkZSBwcmVzZXJ2Ye+/ve+/vW8uIApFc3NlcyB0ZXJtb3MsIG7vv71vIGV4Y2x1c2l2b3MsIG1hbnTvv71tIG9zIGRpcmVpdG9zIGRlIGF1dG9yL2NvcHlyaWdodCwgbWFzIGVudGVuZGUgbyBkb2N1bWVudG8gCmNvbW8gcGFydGUgZG8gYWNlcnZvIGludGVsZWN0dWFsIGRlc3NhIFVuaXZlcnNpZGFkZS4KCiBQYXJhIG9zIGRvY3VtZW50b3MgcHVibGljYWRvcyBjb20gcmVwYXNzZSBkZSBkaXJlaXRvcyBkZSBkaXN0cmlidWnvv73vv71vLCBlc3NlIHRlcm1vIGRlIGxpY2Vu77+9YSAKZW50ZW5kZSBxdWU6CgogTWFudGVuZG8gb3MgZGlyZWl0b3MgYXV0b3JhaXMsIHJlcGFzc2Fkb3MgYSB0ZXJjZWlyb3MsIGVtIGNhc28gZGUgcHVibGljYe+/ve+/vWVzLCBvIHJlcG9zaXTvv71yaW8KcG9kZSByZXN0cmluZ2lyIG8gYWNlc3NvIGFvIHRleHRvIGludGVncmFsLCBtYXMgbGliZXJhIGFzIGluZm9ybWHvv73vv71lcyBzb2JyZSBvIGRvY3VtZW50bwooTWV0YWRhZG9zIGVzY3JpdGl2b3MpLgoKIERlc3RhIGZvcm1hLCBhdGVuZGVuZG8gYW9zIGFuc2Vpb3MgZGVzc2EgdW5pdmVyc2lkYWRlIGVtIG1hbnRlciBzdWEgcHJvZHXvv73vv71vIGNpZW5077+9ZmljYSBjb20gCmFzIHJlc3Ryae+/ve+/vWVzIGltcG9zdGFzIHBlbG9zIGVkaXRvcmVzIGRlIHBlcmnvv71kaWNvcy4KCiBQYXJhIGFzIHB1YmxpY2Hvv73vv71lcyBzZW0gaW5pY2lhdGl2YXMgcXVlIHNlZ3VlbSBhIHBvbO+/vXRpY2EgZGUgQWNlc3NvIEFiZXJ0bywgb3MgZGVw77+9c2l0b3MgCmNvbXB1bHPvv71yaW9zIG5lc3NlIHJlcG9zaXTvv71yaW8gbWFudO+/vW0gb3MgZGlyZWl0b3MgYXV0b3JhaXMsIG1hcyBtYW5077+9bSBhY2Vzc28gaXJyZXN0cml0byAKYW8gbWV0YWRhZG9zIGUgdGV4dG8gY29tcGxldG8uIEFzc2ltLCBhIGFjZWl0Ye+/ve+/vW8gZGVzc2UgdGVybW8gbu+/vW8gbmVjZXNzaXRhIGRlIGNvbnNlbnRpbWVudG8KIHBvciBwYXJ0ZSBkZSBhdXRvcmVzL2RldGVudG9yZXMgZG9zIGRpcmVpdG9zLCBwb3IgZXN0YXJlbSBlbSBpbmljaWF0aXZhcyBkZSBhY2Vzc28gYWJlcnRvLgo=Repositório InstitucionalPUBhttp://192.188.11.11:8080/oai/requestopendoar:19322022-08-08T16:19:12Repositório Institucional da UFBA - Universidade Federal da Bahia (UFBA)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 |
| dc.title.alternative.pt_BR.fl_str_mv |
PLoS Medicine |
| 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 |
| 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, Antônio Ricardo Khouri Santos, Gilvanéia Silva Lopez, Giovanni Alvarez, Carolina Talledo, Michael Gotuzzo, Eduardo Kruschewsky, Ramon de Almeida Castro, Bernardo Galvão Vandamme, Anne Mieke Weyenbergh, Johan Van |
| author_role |
author |
| author2 |
Decanine, Daniele Menezes, Soraya Maria Cunha, Antônio Ricardo Khouri Santos, Gilvanéia Silva Lopez, Giovanni Alvarez, Carolina Talledo, Michael Gotuzzo, Eduardo Kruschewsky, Ramon de Almeida Castro, Bernardo Galvão Vandamme, Anne Mieke Weyenbergh, Johan Van |
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author author author author author author author author author author author author |
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Moens, Britta Decanine, Daniele Menezes, Soraya Maria Cunha, Antônio Ricardo Khouri Santos, Gilvanéia Silva Lopez, Giovanni Alvarez, Carolina Talledo, Michael Gotuzzo, Eduardo Kruschewsky, Ramon de Almeida Castro, Bernardo Galvão Vandamme, Anne Mieke Weyenbergh, Johan Van Moens, Britta Decanine, Daniele Menezes, Soraya Maria Cunha, Antônio Ricardo Khouri Santos, Gilvanéia Silva Lopez, Giovanni Alvarez, Carolina Talledo, Michael Gotuzzo, Eduardo Kruschewsky, Ramon de Almeida Castro, Bernardo Galvão Vandamme, Anne Mieke Weyenbergh, Johan Van |
| description |
p. 1-15 |
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2012 |
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2012-07 |
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2014-08-22T14:38:43Z |
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2014-08-22T14:38:43Z |
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1549-1277 |
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v. 6, n. 7 |
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1549-1277 v. 6, n. 7 |
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