000K utf8 1100 2020$c2020-11-13 1500 eng 2050 urn:nbn:de:hbz:464-20210315-132637-4 2051 10.3390/ijms21228551 3000 Kerber, Evelyn L. 3010 Fandrey, Joachim 3010 Koll, Nora 3010 Padberg, Claudia 3010 Schuetzhold, Vera 3010 Winning, Sandra 4000 Importance of Hypoxia-Inducible Factors (HIF-1 and HIF-2) for the Pathophysiology of Inflammatory Bowel Disease [Kerber, Evelyn L.] 4209 (1) Background: Hypoxia is a common feature of inflammation when hypoxia inducible factors (HIFs) adapt cells to conditions of low oxygen tension and inflammation. We studied the role of HIF-1 and HIF-2 in cells of the myeloid lineage in a mouse model of acute colitis. (2) Methods: Mice with and without a conditional knockout for either Hif-1a or Hif-2a or Hif-1a and Hif-2a in cells of the myeloid lineage were treated with 2.5% dextran sodium sulfate (DSS) for 6 days to induce an acute colitis. We analyzed the course of inflammation with respect to macroscopic (disease activity index) and microscopic (histology score and immunohistochemical staining of immune cells) parameters and quantified the mRNA expression of cytokines and chemokines in the colon and the mesenteric lymph nodes. (3) Results: A conditional knockout of myeloid Hif-1a ameliorated whereas the knockout of Hif-2a aggravated murine DSS colitis by increased recruitment of neutrophils to deeper layers of the colon. This led to higher expression of Il6, Ifng, Cd11c, Cd4, and Cd8 in the colon but also induced anti-inflammatory mediators such as Foxp3 and Il10. A conditional knockout of Hif-1a and Hif-2a did not show any differences compared to wildtype mice. (4) Conclusions: Myeloid HIF-1α and HIF-2α play opposing roles in acute DSS colitis. Thus, not only a cell type specific, but also the isoform specific modulation of HIFs needs to be addressed in attempts to modify HIF for therapeutic purposes. 4950 https://doi.org/10.3390/ijms21228551$xR$3Volltext$534 4950 https://nbn-resolving.org/urn:nbn:de:hbz:464-20210315-132637-4$xR$3Volltext$534 4961 https://duepublico2.uni-due.de/receive/duepublico_mods_00073699 5051 610 5550 HIF-1 5550 Hif-2 5550 IBD 5550 inflammation