| First Author | Bäcker V | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 12 | Pages | e0190074 |
| PubMed ID | 29261815 | Mgi Jnum | J:253688 |
| Mgi Id | MGI:6107181 | Doi | 10.1371/journal.pone.0190074 |
| Citation | Backer V, et al. (2017) Knockdown of myeloid cell hypoxia-inducible factor-1alpha ameliorates the acute pathology in DSS-induced colitis. PLoS One 12(12):e0190074 |
| abstractText | Inflammation and hypoxia are hallmarks of inflammatory bowel disease. Low oxygen levels activate hypoxia-inducible factors as central transcriptional regulators of cellular responses to hypoxia, particularly in myeloid cells where hypoxia-inducible factors control immune cell function and survival. Still, the role of myeloid hypoxia-inducible factor-1 during inflammatory bowel disease remains poorly defined. We therefore investigated the role of hypoxia-inducible factor-1 for myeloid cell function and immune response during colitis. Experimental colitis was induced by administration of 2.5% dextran sulfate sodium to mice with a conditional knockout of hypoxia-inducible factor-1alpha in myeloid cells and their wild type siblings. Murine colon tissue was examined by histologic analysis, immunohistochemistry, and quantitative polymerase chain reaction. Induction of experimental colitis increased levels of hypoxia and accumulation of hypoxia-inducible factor-1alpha positive cells in colon tissue of both treated groups. Myeloid hypoxia-inducible factor-1alpha knockout reduced weight loss and disease activity index when compared to wild type mice. Knockout mice displayed less infiltration of macrophages into intestinal mucosa and reduced mRNA expression of markers for dendritic cells and interleukin-17 secreting T helper cells. Expression of inflammatory and anti-inflammatory cytokines also showed a reduced and delayed induction in myeloid hypoxia-inducible factor-1alpha knockout mice. Our results show a disease promoting role of myeloid hypoxia-inducible factor-1 during intestinal inflammation. This might result from a hypoxia-inducible factor-1 dependent increase in pro-inflammatory interleukin-17 secreting T helper cells in the absence of obvious changes in regulatory T cells. In contrast, knockout mice appear to shift the balance to anti-inflammatory signals and cells resulting in milder intestinal inflammation. |
