title: Imaging Inflammatory Hypoxia in the Murine Gut.
abstract: The inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, result in chronic inflammation to the gastrointestinal tract. In ulcerative colitis, inflammation tends to be more superficial and restricted to the colon; contrastingly, Crohn's disease presents as patchy, more penetrative inflammation that can occur throughout the gastrointestinal tract. Other differences between these diseases include the nature of their respective immune responses-Crohn's disease presents as a Th1 and ulcerative colitis as a Th2-type inflammation. During any inflammatory episode, metabolic demand on the tissue increases accompanying the influx of inflammatory cells, increasing the demand for ATP and oxygen. When availability of oxygen is limiting, tissues become hypoxic, which results in adaptive pathways to enable survival of hypoxic episodes. The primary pathway activated is the HIF (hypoxia inducible factor) transcription factor, which regulates adaptive pathways including genes controlling glycolytic metabolism and angiogenesis. In adequately oxygenated tissues (i.e. normoxia), the HIF protein is constantly produced, but oxygen-dependent enzymes called prolyl-hydroxylases utilize available oxygen to hydroxylate HIF on proline residues, targeting it for ubiquitination and subsequent degradation. Here we describe methods for inducing, visualizing, and quantifying in vivo "inflammatory hypoxia," using the murine gut as a model system.
authors.affiliation: Mucosal Inflammation Program, Department of Medicine, GI Division, University of Colorado - Anschutz Medical Campus, 12700 East 19th Avenue, P15-10026, Mailstop B146, Aurora, CO, 80045, USA.
authors.forename: Alyssa K
authors.initials: AK
authors.lastname: Whitney
authors.affiliation: Mucosal Inflammation Program, Department of Medicine, GI Division, University of Colorado - Anschutz Medical Campus, 12700 East 19th Avenue, P15-10026, Mailstop B146, Aurora, CO, 80045, USA. eric.campbell@ucdenver.edu.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Campbell
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D015687:Cell Hypoxia; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract / Q000276:immunology*; D005786:Gene Expression Regulation; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D051379:Mice; D016707:Tissue Fixation
keywords: HIF; Hypoxia; Hypoxyprobe; Inflammation; ODD-Luc