title: The transcription of the alarmin cytokine interleukin-1 alpha is controlled by hypoxia inducible factors 1 and 2 alpha in hypoxic cells.
abstract: 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.
authors.affiliation: The Shraga Segal Department of Microbiology and Immunology and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev Beer-Sheva, Israel.
authors.forename: Peleg
authors.initials: P
authors.lastname: Rider
authors.forename: Irena
authors.initials: I
authors.lastname: Kaplanov
authors.forename: Marianna
authors.initials: M
authors.lastname: Romzova
authors.forename: Liora
authors.initials: L
authors.lastname: Bernardis
authors.forename: Alex
authors.initials: A
authors.lastname: Braiman
authors.forename: Elena
authors.initials: E
authors.lastname: Voronov
authors.forename: Ron N
authors.initials: RN
authors.lastname: Apte