ICMI 2015

F.10 Loss of myeloid hypoxia inducible factor-1 ameliorates dextran sodium sulfate induced colitis in mice

Friday, July 17, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Veronika Reichmann , Institute of Physiology, Essen, Germany
Sandra Winning , Institut für Physiologie, Universität Duisburg-Essen, Essen, Germany
Joachim Fandrey , Institut für Physiologie, Universität Duisburg-Essen, Essen, Germany
Hypoxia is a hallmark of chronically inflamed tissue when compared to healthy tissue. Under oxygen deficiency, hypoxia, the transcription factor complex hypoxia inducible factor (HIF) regulates expression of genes potentially also involved in the pathogenesis of inflammatory bowel disease (IBD) which embraces Crohn’s disease and ulcerative colitis. Among others HIF-1 is essential for myeloid cell life span and function during inflammation. The complex interplay between hypoxia and inflammation during IBD prompted us to investigate the role of HIF-1 in the pathogenesis of IBD and especially its role in myeloid cells during inflammation.
Mice with a conditional knockout of HIF-1α in myeloid cells (LysMcre/HIF-1α+f/+f) were examined in vivo in a dextran sodium sulfate induced model of inflammatory bowel disease. The disease pattern was described macroscopic, histological and on RNA level. Furthermore, in vitro experiments with bone-marrow-derived macrophages lacking HIF-1α were performed to picture their general behavior. After cultivation under inflammatory and/or hypoxic conditions they were characterized on RNA and protein level.
First experiments provide evidence that LysMcre/HIF-1α+f/+f mice deficient in functional HIF-1 in myeloid cells show a milder form of colitis with less weight loss and lower inflammatory parameters when compared to HIF-1α+f/+f control mice. This could indicate that HIF-1 could act as a proinflammatory regulator of myeloid cells during the course of inflammatory bowel disease.