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https://doi.org/10.1111/cei.12428
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Título: | Regulatory role of PI3K-Akt on the release of IL-1β in peritoneal macrophages from the ascites of cirrhotic patients |
Fecha de publicación: | dic-2014 |
Editorial: | British Society for Immunology |
Cita bibliográfica: | Clinical & Experimental Immunology 178(3):525-36 |
ISSN: | Print: 0009-9104 Electronic: 1365-2249 |
Palabras clave: | Cytokines Inflammation Macrophages Protein kinases Signal transduction |
Resumen: | Great effort has been paid to identify novel targets for pharmaceutical intervention to control inflammation associated with different diseases. We have studied the effect of signalling inhibitors in the secretion of the proinflammatory and profibrogenic cytokine interleukin (IL)-1β in monocyte-derived macrophages (M-DM) obtained from the ascites of cirrhotic patients and compared with those obtained from the blood of healthy donors. Peritoneal M-DM were isolated from non-infected ascites of cirrhotic patients and stimulated in vitro with lipopolysaccharide (LPS) and heat-killed Candida albicans in the presence or absence of inhibitors for c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase kinase 1 (MEK1), p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). The IL1B and CASP1 gene expression were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of IL-1β and caspase-1 were determined by Western blot. IL-1β was also assayed by enzyme-linked immunosorbent assay (ELISA) in cell culture supernatants. Results revealed that MEK1 and JNK inhibition significantly reduced the basal and stimulated IL-1β secretion, while the p38 MAPK inhibitor had no effect on IL-1β levels. On the contrary, inhibition of PI3K increased the secretion of IL-1β from stimulated M-DM. The activating effect of PI3K inhibitor on IL-1β release was mediated mainly by the enhancement of the intracellular IL-1β and caspase-1 content release to the extracellular medium and not by increasing the corresponding mRNA and protein expression levels. These data point towards the role of MEK1 and JNK inhibitors, in contrast to the PI3K-protein kinase B inhibitors, as potential therapeutic tools for pharmaceutical intervention to diminish hepatic damage by reducing the inflammatory response mediated by IL-1β associated with liver failure. |
Autor/es principal/es: | Martínez-Esparza, M. Tapia-Abellán, A. Ruiz Alcaráz, Antonio José Antón, G. Miras-López, M. Francés, R. Such, J. Martínez-Esparza, M. García-Peñarrubia, Pilar |
Facultad/Departamentos/Servicios: | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Bioquímica y Biología Molecular B e Inmunología |
URI: | http://hdl.handle.net/10201/142776 |
DOI: | https://doi.org/10.1111/cei.12428 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 12 |
Derechos: | info:eu-repo/semantics/embargoedAccess |
Descripción: | © 2014 British Society for Immunology. This manuscript version is made available under the CC-BY-NC 4.0 License.http://creativecommons.org/licenses/by-nc/4.0/. This document is the Published version of a Published Work that appeared in final form in American Journal of Clinical and Experimental Immunology. To access the final edited and published work see https://doi.org/10.1111/cei.12428 |
Aparece en las colecciones: | Artículos: Bioquímica y Biología Molecular "B" e Inmunología |
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Fichero | Descripción | Tamaño | Formato | |
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CEI cirrosis 2014.pdf | 612,42 kB | Adobe PDF | ![]() Visualizar/Abrir Solicitar una copia |
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