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Regulatory role of PI3K-protein kinase B on the release of interleukin-1β in peritoneal macrophages from the ascites of cirrhotic patients

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dc.contributor.authorRuiz Alcaraz, Antonio José
dc.contributor.authorAntón, G.
dc.contributor.authorMiras López, M.
dc.contributor.authorFrancés, R.
dc.contributor.authorSuch, J.
dc.contributor.authorMartínez-Esparza Alvargonzález, María Concepción
dc.contributor.authorGarcía Peñarrubia, María del Pilar
dc.contributor.authorTapia Abellán, Ana
dc.contributor.departmentBioquímica y Biología Molecular B e Inmunología
dc.date.accessioned2024-07-02T08:22:06Z
dc.date.available2024-07-02T08:22:06Z
dc.date.copyright© 2014 British Society for Immunology.
dc.date.issued2014-07-29
dc.description.abstractGreat 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.es
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dc.identifier.citationClinical & Experimental Immunology 178(3):525-36
dc.identifier.doihttps://doi.org/10.1111/cei.12428
dc.identifier.issnPrint: 0009-9104
dc.identifier.issnElectronic: 1365-2249
dc.identifier.urihttp://hdl.handle.net/10201/142776
dc.languageenges
dc.publisherBritish Society for Immunologyes
dc.relationThis study was funded by grant 11926/PI/09 from the Fundación Séneca, Comunidad Autónoma de la Región de Murcia, Spain. Ana Tapia-Abellán was supported by the Fundación Séneca (12302/FPI/09), Comunidad Autónoma de la Región de Murcia, Spain.es
dc.relation.publisherversionhttps://academic.oup.com/cei/article-abstract/178/3/525/6421280
dc.rightsinfo:eu-repo/semantics/restrictedAccesses
dc.subjectCytokineses
dc.subjectInflammationes
dc.subjectMacrophageses
dc.subjectProtein kinaseses
dc.subjectSignal transductiones
dc.titleRegulatory role of PI3K-protein kinase B on the release of interleukin-1β in peritoneal macrophages from the ascites of cirrhotic patientses
dc.typeinfo:eu-repo/semantics/articlees
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublicationes
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