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The Importance of Hypoxia-Inducible Factors (HIF-1 and HIF-2) for the Pathophysiology of Inflammatory Bowel Disease

Institute for Physiology, University of Duisburg-Essen, 45147 Essen, Germany
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Int. J. Mol. Sci. 2020, 21(22), 8551; https://doi.org/10.3390/ijms21228551
Received: 12 October 2020 / Revised: 9 November 2020 / Accepted: 10 November 2020 / Published: 13 November 2020
(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. View Full-Text
Keywords: IBD; inflammation; HIF-1; HIF-2 IBD; inflammation; HIF-1; HIF-2
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MDPI and ACS Style

Kerber, E.L.; Padberg, C.; Koll, N.; Schuetzhold, V.; Fandrey, J.; Winning, S. The Importance of Hypoxia-Inducible Factors (HIF-1 and HIF-2) for the Pathophysiology of Inflammatory Bowel Disease. Int. J. Mol. Sci. 2020, 21, 8551. https://doi.org/10.3390/ijms21228551

AMA Style

Kerber EL, Padberg C, Koll N, Schuetzhold V, Fandrey J, Winning S. The Importance of Hypoxia-Inducible Factors (HIF-1 and HIF-2) for the Pathophysiology of Inflammatory Bowel Disease. International Journal of Molecular Sciences. 2020; 21(22):8551. https://doi.org/10.3390/ijms21228551

Chicago/Turabian Style

Kerber, Evelyn L.; Padberg, Claudia; Koll, Nora; Schuetzhold, Vera; Fandrey, Joachim; Winning, Sandra. 2020. "The Importance of Hypoxia-Inducible Factors (HIF-1 and HIF-2) for the Pathophysiology of Inflammatory Bowel Disease" Int. J. Mol. Sci. 21, no. 22: 8551. https://doi.org/10.3390/ijms21228551

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