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| Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
| Campo DC | Valor | Lengua/Idioma |
|---|---|---|
| dc.contributor.author | Reboredo, Mercedes | - |
| dc.contributor.author | De Las Rivas, Javier | - |
| dc.date.accessioned | 2012-11-21T09:32:54Z | - |
| dc.date.available | 2012-11-21T09:32:54Z | - |
| dc.date.issued | 2008 | - |
| dc.identifier | doi: 10.1038/sj.gt.3303073 | - |
| dc.identifier | issn: 0969-7128 | - |
| dc.identifier | e-issn: 1476-5462 | - |
| dc.identifier.citation | Gene Therapy 15: 277-288 (2008) | - |
| dc.identifier.uri | http://hdl.handle.net/10261/60694 | - |
| dc.description | El pdf del artículo es la versión de autor.-- et al. | - |
| dc.description.abstract | Drug-inducible systems allow modulation of the duration and intensity of cytokine expression in liver immuno-based gene therapy protocols. However, the biological activity of the transgene may influence their function. We have analyzed the kinetics of interleukin-12 (IL-12) expression controlled by the doxycycline (Dox)- and the mifepristone (Mif)-dependent systems using two long-term expressing vectors directed to liver: a plasmid administered by hydrodynamic injection and a high-capacity adenoviral vector. Daily administration of Dox or Mif was associated with a progressive loss of inducibility and a decrease of murine IL-12 production. This inhibition occurred at the transcriptional level and was probably caused by an interferon (IFN)-γ-mediated downmodulation of liver-specific promoters that control the expression of transactivators in these systems. Genome-wide expression microarrays studies revealed a parallel downregulation of liver-specific genes in mice overexpressing murine IL-12. However, a promoter naturally induced by IL-12 was also inhibited by this cytokine when placed in a plasmid vector. Interestingly, treatment with sodium butyrate, a class I/II histone deacetylase inhibitor, was able to rescue liver-specific promoter activity solely in the vector. We conclude that biologically active IL-12 can transiently inhibit the function of drug-inducible systems in non-integrative DNA vectors by reducing promoter activity, probably through IFN-γ and protein deacetylation-dependent mechanisms. | - |
| dc.description.sponsorship | This project was founded through the UTE project CIMA, DIGNA Biotech and Grants from Education Department, Gobierno de Navarra and Fondo de Investigación Sanitaria (FIS) and CIBERehd. RHA is a recipient of Ramón y Cajal research contract. MGK is a recipient of an FIS research contract. IM is a recipient of a Torres Quevedo contract. | - |
| dc.language.iso | eng | - |
| dc.publisher | Nature Publishing Group | - |
| dc.rights | openAccess | - |
| dc.title | Interleukin-12 inhibits liver-specific drug-inducible systems in vivo | - |
| dc.type | artículo | - |
| dc.identifier.doi | 10.1038/sj.gt.3303073 | - |
| dc.relation.publisherversion | http://dx.doi.org/10.1038/sj.gt.3303073 | - |
| dc.date.updated | 2012-11-21T09:32:54Z | - |
| dc.description.version | Peer Reviewed | - |
| dc.identifier.pmid | 18033307 | - |
| dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
| item.fulltext | With Fulltext | - |
| item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
| item.cerifentitytype | Publications | - |
| item.openairetype | artículo | - |
| item.grantfulltext | open | - |
| item.languageiso639-1 | en | - |
| Aparece en las colecciones: | (IBMCC) Artículos | |
Ficheros en este ítem:
| Fichero | Descripción | Tamaño | Formato | |
|---|---|---|---|---|
| INTERLEUKIN-12.pdf | 3,33 MB | Adobe PDF |  Visualizar/Abrir |
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