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Título: | Sirtuin 1 is a key regulator of the interleukin-12 p70/interleukin-23 balance in human dendritic cells |
Autor: | Alvarez, Yolanda CSIC ORCID; Rodríguez Peña, Mario CSIC ORCID CVN ; Municio, Cristina CSIC ORCID; Hugo, Etzel; Alonso, Sara CSIC ORCID CVN; Ibarrola, Nieves CSIC ; Fernández, Nieves CSIC ORCID; Sánchez Crespo, Mariano CSIC ORCID | Palabras clave: | NF-κB (NF-KB) Sirtuins NAD Histone deacetylases Dendritic cells |
Fecha de publicación: | 2012 | Editor: | American Society for Biochemistry and Molecular Biology | Citación: | Journal of Biological Chemistry 287(42): 35689-35701 (2012) | Resumen: | Stimulation of human dendritic cells with the fungal surrogate zymosan produces IL-23 and a low amount of IL-12 p70. Trans-repression of il12a transcription, which encodes IL-12 p35 chain, by proteins of the Notch family and lysine deacetylation reactions have been reported as the underlying mechanisms, but a number of questions remain to be addressed. Zymosan produced the location of sirtuin 1 (SIRT1) to the nucleus, enhanced its association with the il12a promoter, increased the nuclear concentration of the SIRT1 co-substrate NAD +, and decreased chromatin accessibility in the nucleosome-1 of il12a, which contains a κB-site. The involvement of deacetylation reactions in the inhibition of il12a transcription was supported by the absence of Ac-Lys-14-histone H3 in dendritic cells treated with zymosan upon coimmunoprecipitation of transducin- like enhancer of split. In contrast, we did not obtain evidence of a possible effect of SIRT1 through the deacetylation of c-Rel, the central element of the NF-κB family involved in il12a regulation. These data indicate that an enhancement of SIRT1 activity in response to phagocytic stimuli may reduce the accessibility of c-Rel to the il12a promoter and its transcriptional activation, thus regulating the IL-12 p70/IL-23 balance and modulating the ongoing immune response. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. | URI: | http://hdl.handle.net/10261/116657 | DOI: | 10.1074/jbc.M112.391839 | Identificadores: | doi: 10.1074/jbc.M112.391839 issn: 0021-9258 e-issn: 1083-351X |
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Sirtuin 1 Is a Key Regulator_Alvarez_2012.pdf | 2,47 MB | Adobe PDF | Visualizar/Abrir |
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