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M1 Macrophages Activate Notch Signalling in Epithelial Cells: Relevance in Crohn's Disease

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M1 Macrophages Activate Notch Signalling in Epithelial Cells: Relevance in Crohn's Disease

dc.contributor.author	Ortiz Masiá, María Dolores
dc.contributor.author	Cosín Roger, Jesús
dc.contributor.author	Calatayud Romero, Sara
dc.contributor.author	Hernández, C.
dc.contributor.author	Alós Company, Rafael
dc.contributor.author	Hinojosa, Joaquin
dc.contributor.author	Esplugues Mota, Juan Vicente
dc.contributor.author	Barrachina Sancho, María Dolores
dc.date.accessioned	2016-06-27T11:32:16Z
dc.date.available	2016-06-27T11:32:16Z
dc.date.issued	2016
dc.identifier.citation	Ortiz-Masiá, María Dolores; Cosín Roger, Jesús; Calatayud Romero, Sara; Hernández, C.; Alós, R.; Hinojosa, J.; Esplugues, Juan Vicente; Barrachina Sancho, María Dolores (2016) M1 Macrophages Activate Notch Signalling in Epithelial Cells: Relevance in Crohn's Disease Journal Of Crohns & Colitis
dc.identifier.uri	http://hdl.handle.net/10550/54263
dc.description.abstract	Background: The Notch signalling pathway plays an essential role in mucosal regeneration, which constitutes a key goal of Crohn's disease (CD) treatment. Macrophages coordinate tissue repair and several phenotypes have been reported which differ in the expression of surface proteins, cytokines and hypoxia-inducible factors (HIFs). We analysed the role of HIFs in the expression of Notch ligands in macrophages and the relevance of this pathway in mucosal regeneration. Methods: Human monocytes and U937-derived macrophages were polarized towards the M1 and M2 phenotypes and the expression levels of HIF-1α, HIF-2α, Jagged 1 (Jag1) and delta-like 4 (Dll4) were evaluated. The effects of macrophages on the expression of hairy and enhancer of split-1 (HES1, the main target of Notch signalling) and intestinal alkaline phosphatase (IAP, enterocyte marker) in epithelial cells in co-culture were also analysed. Phenotype macrophage markers and Notch signalling were evaluated in the mucosa of CD patients. Results: M1 macrophages were associated with HIF-1-dependent induction of Jag1 and Dll4, which increased HES1 protein levels and IAP activity in co-cultured epithelial cells. In the mucosa of CD patients a high percentage of M1 macrophages expressed both HIF-1α and Jag1 while M2 macrophages mainly expressed HIF-2α and we detected a good correlation between the ratio of M1/M2 macrophages and both HES1 and IAP protein levels. Conclusion: M1, but not M2, macrophages are associated with HIF-1-dependent induction of Notch ligands and activation of epithelial Notch signalling pathway. In the mucosa of chronic CD patients, the prevalence of M2 macrophages is associated with diminution of Notch signalling and impaired enterocyte differentiation. Key Words: MacrophagesCrohn's diseasemucosal healingNotch signalling
dc.language.iso	eng
dc.relation.ispartof	Journal Of Crohns & Colitis, 2016
dc.subject	Farmacologia
dc.subject	Aparell digestiu Malalties
dc.subject	Recte Malalties
dc.title	M1 Macrophages Activate Notch Signalling in Epithelial Cells: Relevance in Crohn's Disease
dc.type	journal article	es_ES
dc.date.updated	2016-06-27T11:32:17Z
dc.identifier.doi	10.1093/ecco-jcc/jjw009
dc.identifier.idgrec	111356
dc.rights.accessRights	open access	es_ES