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Título: | Role of MAP Kinases and PI3K-Akt on the cytokine inflammatory profile of peritoneal macrophages from ascites of cirrhotic patients |
Fecha de publicación: | 20-ene-2013 |
Editorial: | Wiley |
Cita bibliográfica: | Liver International 33(4): 552-60 |
ISSN: | 1478-3223 |
Palabras clave: | Ascites Cirrhosis Cytokines Macrophages MAP kinases PI3K |
Resumen: | Aims: Several new approaches targeting inflammation associated with different diseases are in clinical development. Objective: To explore the role played by MAPK and PI3K-Akt pathways on the release of cytokines in monocyte-derived macrophages (M-DM) obtained from the ascites of cirrhotic patients to identify novel targets for pharmaceutical intervention to prevent hepatic damage. Methods: M-DM were isolated from the ascites of cirrhotic patients and stimulated in vitro with LPS and heat-killed Candida albicans in the presence or absence of the inhibitors for MEK1, p38 MAPK, JNK and PI3K. The MAPK phosphorylation levels were determined by Western Blot. Cell culture supernatants were assayed by ELISA for TNF-α, IL-6 and IL-10. Results: The release of the pro-inflammatory cytokines IL-6 and TNF-α at baseline was more effectively reduced by the MAPK inhibitors, while the basal IL-10 anti-inflammatory cytokine secretion was only and strongly (90.3%) affected by the PI3K inhibitor. The incubation of peritoneal M-DM in the presence of LPS and C. albicans increased the release of IL-6, TNF-α and IL-10. LPS-induced pro-inflammatory cytokines secretion was more sensitive to MAPK inhibitors, whereas that induced by C. albicans was more susceptible to inhibition of PI3K. Finally, inhibition of PI3K almost completely suppressed the secretion of IL-10 in stimulated M-DM. Conclusions: These results demonstrate that pro-inflammatory cytokines release in M-DM from this clinical setting strongly depends on the MAPK signalling pathways, differs depending on the microbial stimulus added and confirms the prominent role of the PI3K-Akt pathway in the modulation of IL-10-mediated anti-inflammatory function. |
Autor/es principal/es: | Martínez-Esparza, M. Tapia-Abellán, Ana Ruiz-Alcaraz, Antonio J. Hernández-Caselles, Trinidad Such, José Francés, Rubén García-Penarrubia, 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/10201/142798 |
DOI: | https://doi.org/10.1111/liv.12072 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 9 |
Derechos: | info:eu-repo/semantics/embargoedAccess |
Descripción: | © 2013 John Wiley & Sons A/S. This document is the Published version of a Published Work that appeared in final form in Liver International. To access the final edited and published work see https://doi.org/10.1111/liv.12072 |
Aparece en las colecciones: | Artículos: Bioquímica y Biología Molecular "B" e Inmunología |
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