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

Journal of Crohn's & Colitis
D Ortiz-MasiáM D Barrachina

Abstract

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. 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. 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 ...Continue Reading

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Citations

Jan 6, 2018·Journal of Crohn's & Colitis·Pedro SalvadorSara Calatayud
Apr 11, 2018·Breast Cancer Research : BCR·Ramon M CabreraJeffrey E Segall
Mar 21, 2020·International Journal of Cancer. Journal International Du Cancer·Martina RaudenskaMichal Masarik
Jul 31, 2019·Journal of Crohn's & Colitis·Dolores Ortiz-MasiàMaría D Barrachina
Mar 7, 2019·Clinical Journal of Gastroenterology·Tomoya IidaHiroshi Nakase
Oct 15, 2019·Frontiers in Immunology·Jesús Cosin-RogerMª Dolores Barrachina
Aug 3, 2021·Frontiers in Cellular and Infection Microbiology·Sudha B SinghHenry C Lin

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