Inflammatory bowel disease (IBD) comprises Crohn's disease and ulcerative colitis and affects up to 1 in 200 of individuals of Northern European region. From the literature it is known that chronically inflamed tissue sites are hypoxic relative to normal healthy tissue. The hypoxia inducible factor (HIF) regulates hypoxia-induced expression of genes and has been shown to be involved in the pathogenesis of IBD. HIF-1 is also essential for myeloid cell function during inflammation. The complex interplay between hypoxia and inflammation during IBD prompted us to investigate the role of HIF-1 and HIF-2 in the pathology of IBD and especially their role in myeloid cells during inflammation.

Mice with a knockout of HIF-1α or HIF-2α in myeloid cells (LysMcre/HIF-1α^+f/+f, LysMcre/HIF-2α^+f/+f) were examined in vivo in a DSS-induced model of IBD. Furthermore, bone-marrow-derived macrophages (BMDM) lacking HIF-1α or HIF-2α were analyzed under inflammatory and/or hypoxic conditions.

First experiments provide evidence that LysMcre/HIF-1α^+f/+f mice show a less severe disease with reduced weight loss and reduced inflammatory parameters in comparison to HIF-1α^+f/+f mice, - expressing functional HIF-1α.

The transcription factor HIF-1 seems to be a critical factor in myeloid cells during the clinical course of IBD.