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Given the existence of the oxygen gradient in the intestinal epithelium and that inflammation further contributes to the tissue hypoxia, we investigated the role of hypoxia-inducible factor (HIF), a transcription factor activated under hypoxic conditions in myeloid cells, in the progression of IBD. To do this, we utilized myeloid-specific knockout (KO) mice targeting HIF pathways, created by a Cre-loxP system with human MRP8 (hMRP8), an intracellular calcium-binding protein, as the myeloid promoter. By feeding 5% dextran sodium sulfate (DSS) to hMRP8 von Hippel Lindau (Vhl) KO mice, in which HIF-1\u03b1 and HIF-2\u03b1 are constitutively activated in myeloid cells, we found that these mice were highly susceptible to DSS-induced colitis, demonstrating greater body weight loss, increased mortality, faster onset of rectal bleeding, shortened colon length, and increased CD11b- or Gr-1-positive myeloid cells in the colon compared with wild-type (WT) mice. These parameters were restored to, if not better than, the WT levels when we examined hMRP8 Hif-1a KO mice upon 5% DSS feeding. hMRP8 Hif-2a KO mice, on the other hand, exhibited a similar degree of DSS-induced colitis to that of WT mice. Lastly, when DSS was given together with azoxymethane to induce tumorigenesis in the colon, we found that hMRP8 Hif-1a KO mice exhibited comparable levels of colorectal tumors to those of WT mice, indicating that HIF-1\u03b1 in myeloid cells is dispensable for tumorigenesis. Collectively, our results suggest that HIF-1\u03b1 activation in myeloid cells critically regulates IBD progression.<\/jats:p>","DOI":"10.1242\/dmm.033241","type":"journal-article","created":{"date-parts":[[2018,7,2]],"date-time":"2018-07-02T07:35:12Z","timestamp":1530516912000},"source":"Crossref","is-referenced-by-count":38,"title":["HIF-1\u03b1 activation in myeloid cells accelerates dextran sodium sulfate-induced colitis progression in mice"],"prefix":"10.1242","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5646-606X","authenticated-orcid":false,"given":"Young-Eun","family":"Kim","sequence":"first","affiliation":[{"name":"Pohang University of Science and Technology (POSTECH) 1 Division of Integrative Biosciences and Biotechnology , , 77 Cheong Am-Ro, Nam-Gu, Pohang, Gyeongbuk 37673 , South 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