L-16 - Oxygen homeostasis in intestinal health and inflammation

• Published in: Free radical biology & medicine Vol. 120; p. S10
• Main Author: Campbell, Eric
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 20.05.2018
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2018.04.045

A steep oxygen gradient exists between the vascular bed of the colonic mucosa and the anoxic lumen harboring the microbiota. Host responses to injury or infection include recruitment of immune cells and localized production of reactive oxygen species, resulting in tissue injury. The influx and activity of immune cells enhances the metabolic demand of the tissue. In order to restore equilibrium, the mucosa must adapt to the inflammatory environment and pave the way for resolution. Both diminished oxygen availability and reactive oxygen species result in tissue hypoxia and inhibition of the prolyl hydroxylase (PHD) enzymes, leading to stabilization of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). Treatment of mice with PHD inhibitors (PHDi) leads to stabilization of epithelial HIF-1α and regulation of hypoxia-responsive genes that promote mucosal protection. Interestingly, enhanced staining for goblet cell mucus was observed following in vivo administration of PHDi. Furthermore, mice lacking intestinal epithelial HIF -1α exhibited diminished thickness of the sterile mucus. We conclude that epithelial HIF-1α promotes goblet cell function, regulating intestinal mucus, which may contribute to the mucosal-protective role of HIF in promoting mucosal homeostasis.