Interleukin-1beta and tumor necrosis factor-alpha stimulate DNA binding of hypoxia-inducible factor-1
- PMID: 10477681
Interleukin-1beta and tumor necrosis factor-alpha stimulate DNA binding of hypoxia-inducible factor-1
Abstract
The rate of transcription of several genes encoding proteins involved in O(2) and energy homeostasis is controlled by hypoxia-inducible factor-1 (HIF-1), a heterodimeric DNA binding complex composed of alpha and beta subunits. HIF-1 is considered the primary trans-acting factor for the erythropoietin (EPO) and vascular endothelial growth factor (VEGF) genes. Since EPO gene expression is inhibited by the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), while no such effect has been reported with respect to the VEGF gene, we investigated the effects of IL-1beta and TNF-alpha on the activation of the HIF-1 DNA-binding complex and the amount of HIF-1alpha protein in human hepatoma cells in culture. Under normoxic conditions, both cytokines caused a moderate activation of HIF-1 DNA binding. In hypoxia, cytokines strongly increased HIF-1 activity compared with the effect of hypoxia alone. Only IL-1beta increased HIF-1alpha protein levels. In transient transfection experiments, HIF-1-driven reporter gene expression was augmented by cytokines only under hypoxic conditions. In contrast to their effect on EPO synthesis, neither IL-1beta nor TNF-alpha decreased VEGF production. The mRNA levels of HIF-1alpha and VEGF were unaffected. Thus, cytokine-induced inhibition of EPO production is not mediated by impairment of HIF-1 function. We propose that HIF-1 may be involved in modulating gene expression during inflammation.
Similar articles
-
HIF-1: the knowns and unknowns of hypoxia sensing.Acta Biochim Pol. 2004;51(3):563-85. Acta Biochim Pol. 2004. PMID: 15448722 Review.
-
Hypoxia and interleukin-1beta stimulate vascular endothelial growth factor production in human proximal tubular cells.Kidney Int. 2000 Jul;58(1):43-50. doi: 10.1046/j.1523-1755.2000.00139.x. Kidney Int. 2000. PMID: 10886548
-
Co-transactivation of the 3' erythropoietin hypoxia inducible enhancer by the HIF-1 protein.Blood Cells Mol Dis. 1997 Aug;23(2):169-76. doi: 10.1006/bcmd.1997.0134. Blood Cells Mol Dis. 1997. PMID: 9236155
-
Structural and functional analysis of hypoxia-inducible factor 1.Kidney Int. 1997 Feb;51(2):553-5. doi: 10.1038/ki.1997.77. Kidney Int. 1997. PMID: 9027737 Review.
-
Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1.Mol Cell Biol. 1996 Sep;16(9):4604-13. doi: 10.1128/MCB.16.9.4604. Mol Cell Biol. 1996. PMID: 8756616 Free PMC article.
Cited by
-
The Role of Oxygen Homeostasis and the HIF-1 Factor in the Development of Neurodegeneration.Int J Mol Sci. 2024 Apr 23;25(9):4581. doi: 10.3390/ijms25094581. Int J Mol Sci. 2024. PMID: 38731800 Free PMC article. Review.
-
Exposure to normobaric hypoxia shapes the acute inflammatory response in human whole blood cells in vivo.Pflugers Arch. 2024 May 7. doi: 10.1007/s00424-024-02969-2. Online ahead of print. Pflugers Arch. 2024. PMID: 38714572
-
Vascular leak in sepsis: physiological basis and potential therapeutic advances.Crit Care. 2024 Mar 23;28(1):97. doi: 10.1186/s13054-024-04875-6. Crit Care. 2024. PMID: 38521954 Free PMC article. Review.
-
Protein kinase B/AKT phosphorylates hypoxia-inducible factor-3α1 in response to insulin, promoting cell growth and migration.Front Cell Dev Biol. 2023 Nov 9;11:1250000. doi: 10.3389/fcell.2023.1250000. eCollection 2023. Front Cell Dev Biol. 2023. PMID: 38020884 Free PMC article.
-
Sensing the oxygen and temperature in the adipose tissues - who's sensing what?Exp Mol Med. 2023 Nov;55(11):2300-2307. doi: 10.1038/s12276-023-01113-x. Epub 2023 Nov 1. Exp Mol Med. 2023. PMID: 37907745 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials