TY - JOUR
T1 - The transcription of the alarmin cytokine interleukin-1 alpha is controlled by hypoxia inducible factors 1 and 2 alpha in hypoxic cells
AU - Rider, Peleg
AU - Kaplanov, Irena
AU - Romzova, Marianna
AU - Braiman, Liora
AU - Braiman, Alex
AU - Voronov, Elena
AU - Apte, Ron N.
PY - 2012/12/1
Y1 - 2012/12/1
N2 - During hypoxia, cells undergo transcriptional changes to adjust to metabolic stress, to pro- mote 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 condi- tions, 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, how- ever, 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.
AB - During hypoxia, cells undergo transcriptional changes to adjust to metabolic stress, to pro- mote 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 condi- tions, 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, how- ever, 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.
KW - Alarmin
KW - Cytokines and inflammation
KW - DAMPs
KW - HIF-1α
KW - HIF-2
KW - IL-1
KW - Sterile inflammation
UR - http://www.scopus.com/inward/record.url?scp=84874269082&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2012.00290
DO - 10.3389/fimmu.2012.00290
M3 - Article
AN - SCOPUS:84874269082
SN - 1664-3224
VL - 3
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - SEP
M1 - Article 290
ER -