The transcription of the alarmin cytokine interleukin-1 alpha is controlled by hypoxia inducible factors 1 and 2 alpha in hypoxic cells

• Published in: Frontiers in immunology Vol. 3; p. 290
• Main Authors: Rider, Peleg, Kaplanov, Irena, Romzova, Marianna, Bernardis, Liora, Braiman, Alex, Voronov, Elena, Apte, Ron N
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 2012; Frontiers Media S.A
• Subjects: alarmin; Cytokines and inflammation; DAMPs; HIF-1α; IL-1; Immunology; Sterile Inflammation; sterile inflammation; HIF-2; alarmin; cytokines and inflammation; IL-1; HIF-1α; DAMPs
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2012.00290

During hypoxia, cells undergo transcriptional changes to adjust to metabolic stress, to promote cell survival, and to induce pro-angiogenic factors. Hypoxia-induced factors (HIFs) regulate these transcriptional alterations. Failure to restore oxygen levels results in cell death by necrosis. IL-1α is one of the most important mediators of sterile inflammation following hypoxia-mediated necrosis. During hypoxia, IL-1α is up-regulated and released from necrotic cells, promoting the initiation of sterile inflammation. This study examined the role of IL-1α transcription in initiation of hypoxic stress and the correlation between IL-1α transcription and HIFα factors. In an epithelial cell line cultured under hypoxic conditions, IL-1α transcription was up-regulated in a process mediated and promoted by HIFα factors. IL-1α transcription was also up-regulated in hypoxia in a fibroblast cell line, however, in these cells, HIFα factors inhibited the elevation of transcription. These data suggest that HIFα factors play a significant role in initiating sterile inflammation by controlling IL-1α transcription during hypoxia in a differential manner, depending on the cell type.