| Autor: |
De Galan C; Department of Internal Medicine and Paediatrics, Ghent University, 9000 Ghent, Belgium.; Ghent Gut Inflammation Group (GGIG), Ghent University, 9000 Ghent, Belgium.; VIB Centre for Inflammation Research, 9000 Ghent, Belgium., De Vos M; Department of Internal Medicine and Paediatrics, Ghent University, 9000 Ghent, Belgium.; Ghent Gut Inflammation Group (GGIG), Ghent University, 9000 Ghent, Belgium., Hindryckx P; Department of Internal Medicine and Paediatrics, Ghent University, 9000 Ghent, Belgium.; Department of Gastroenterology, Ghent University Hospital, 9000 Ghent, Belgium., Laukens D; Department of Internal Medicine and Paediatrics, Ghent University, 9000 Ghent, Belgium.; Ghent Gut Inflammation Group (GGIG), Ghent University, 9000 Ghent, Belgium.; VIB Centre for Inflammation Research, 9000 Ghent, Belgium., Van Welden S; Department of Internal Medicine and Paediatrics, Ghent University, 9000 Ghent, Belgium.; Ghent Gut Inflammation Group (GGIG), Ghent University, 9000 Ghent, Belgium.; VIB Centre for Inflammation Research, 9000 Ghent, Belgium. |
| Abstrakt: |
Environmental hypoxia and hypoxia-induced signalling in the gut influence inflammatory bowel disease pathogenesis, however data is limited to colitis. Hence, we investigated the effect of environmental hypoxia and immune cell-specific deletion of oxygen sensor prolyl hydroxylase (PHD) 1 in a Crohn's like ileitis mouse model. Therefore, 5-week-old C57/BL6 TNF ∆ARE/+ mice and wildtype (WT) littermates were housed in normoxia (21% O 2 ) or hypoxia (8% O 2 ) for 10 weeks. Systemic inflammation was assessed by haematology. Distal ileal hypoxia was evaluated by pimonidazole staining. The ileitis degree was scored on histology, characterized via qPCR and validated in haematopoietic Phd1-deficient TNF ∆ARE/+ mice. Our results demonstrated that hypoxia did not impact body weight evolution in WT and TNF ∆ARE/+ mice. Hypoxia increased red blood cell count, haemoglobin, haematocrit and increased pimonidazole intensity in the ileum. Interestingly, hypoxia evoked an increase in circulatory monocytes, ileal mononuclear phagocytes and proinflammatory cytokine expression in WT mice. Despite these alterations, no histological or ileal gene expression differences could be identified between TNF ∆ARE/+ mice housed in hypoxia versus normoxia nor between haematopoietic Phd1-deficient TNF ∆ARE/+ and their WT counterparts. Therefore, we demonstrated for the first time that long-term environmental hypoxia or haematopoietic Phd1-deletion does not impact experimental ileitis development. |
