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Peritoneal macrophage priming in cirrhosis is related to ERK phosphorylation and IL-6 secretion.

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dc.contributor.authorRuiz Alcaraz, Antonio José
dc.contributor.authorMartínez-Esparza Alvargonzález, María Concepción
dc.contributor.authorCaño, Rocío
dc.contributor.authorHernández Caselles, Trinidad
dc.contributor.authorRicarti, Chiara
dc.contributor.authorLlanos, Lucía
dc.contributor.authorZapater, Pedro
dc.contributor.authorMartín-Orozco Santiago, María Elena
dc.contributor.authorPérez Mateo, Miguel
dc.contributor.authorSuch, José
dc.contributor.authorGarcía Peñarrubia, María del Pilar
dc.contributor.authorFrancés, Rubén
dc.contributor.authorTapia Abellán, Ana
dc.contributor.departmentBioquímica y Biología Molecular B e Inmunología
dc.date.accessioned2024-07-03T08:02:06Z
dc.date.available2024-07-03T08:02:06Z
dc.date.copyright© 2010 The Authors.
dc.date.issued2010-08-19
dc.description.abstractBackground: Bacterial infections are common complications arising in patients with cirrhosis and ascites. Translocation of bacterial DNA is a dynamic process that is associated with an increased inflammatory response and a poor prognosis in this setting. The aim of this study was to study whether peritoneal macrophages remain in a chronic primed status to allow a rapid response to subsequent events of bacterial translocation. Patients and methods: Peritoneal monocyte-derived macrophages were isolated from 25 patients with cirrhosis and non-infected ascites and compared with donor's blood monocytes. Activation cell-surface markers were screened using flow-cytometry, and the phosphorylation state of ERK 1/2, p38 MAP Kinase, PKB/Akt and transcription factors c-Jun and p65 NFκB were evaluated using Western blot. Synthesis of tumour necrosis factor alpha, interleukin 6 (IL-6) and interleukin-10 (IL-10) at baseline and in response to bacterial stimuli was evaluated using ELISA. Results: A high expression of CD54, CD86 and HLA-DR at baseline was displayed by peritoneal macrophages. Increased phosphorylated levels of ERK1/2, protein kinase B (PKB) and c-Jun, together with IL-6 production, were observed in peritoneal macrophages at baseline compared with donors' blood monocytes. A positive correlation was established between basal IL-6 levels and extracellular signal-regulated kinase (ERK) phosphorylation in peritoneal macrophages from patients with cirrhosis (r=0·9; P=0·005). Addition of lipopolysaccharide induced higher phosphorylation levels of all studied signalling intermediates than synthetic-oligodeoxydinucleotides, but similar end-stage p65 NFκB. Conclusions: A sustained immune response is present in ascitic fluid of cirrhotic patients, even in the temporal absence of bacterial antigens. This would facilitate a fast response, probably controlled by IL-6, against repeated bacterial-DNA translocation or in liver chronic inflammation.es
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dc.identifier.citationEuropean Journal of Clinical Investigation. 2011, Vol. 41 (1), pp. 8-15
dc.identifier.doihttps://doi.org/10.1111/j.1365-2362.2010.02368.x
dc.identifier.eissn1365-2362
dc.identifier.issn0014-2972
dc.identifier.urihttp://hdl.handle.net/10201/142823
dc.languageenges
dc.publisherWileyes
dc.relationThis study was funded by grants PI06 ⁄ 1453, PI06 ⁄ 0006 and CP05 ⁄ 0005 from Instituto de Salud Carlos III, Madrid, Spain and 11926 ⁄ PI ⁄ 09 from Fundación Séneca (CARM, Murcia, Spain). Ana Tapia-Abellán has a PhD fellowship from Fundación Séneca (12302/FPI/09).es
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/doi/10.1111/j.1365-2362.2010.02368.xes
dc.rightsinfo:eu-repo/semantics/restrictedAccesses
dc.subjectAscitic fluides
dc.subjectCirrhosises
dc.subjectCytokineses
dc.subjectMacrophageses
dc.subjectMAP kinaseses
dc.titlePeritoneal macrophage priming in cirrhosis is related to ERK phosphorylation and IL-6 secretion.es
dc.typeinfo:eu-repo/semantics/articlees
dc.type.versioninfo:eu-repo/semantics/publishedVersion
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