ArticleFree radical biology & medicine2011
Opposite effects of HIF-1α and HIF-2α on the regulation of IL-8 expression in endothelial cells.
Article in Free radical biology & medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 92 citations in OpenAlex.
- Effects ofMolecules (Basel, Switzerland) · 2026Article
- Research progress on vasculogenic mimicry in colorectal cancer: mechanisms and therapeutic.Cell division · 2026Review
- Serine/threonine kinase 33 mediates thrombin-induced interleukin-8 release from human lung epithelial cells in severe asthma.Respiratory research · 2025Article
- The Role of Interleukin-8 (IL-8) in Treatment-Resistant Depression: A Review of Mechanisms, Biomarker Potential, and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Review
- HIF-2α accumulation in human monocytes upon transfer of hypoxia-associated miRNAs via plasma-derived small extracellular vesicles from head and neck cancer patients.Frontiers in oncology · 2025Article
- Endothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway.Frontiers in physiology · 2024Article
- Interaction and Collaboration of SP1, HIF-1, and MYC in Regulating the Expression of Cancer-Related Genes to Further Enhance Anticancer Drug Development.Current issues in molecular biology · 2023Review
- Salmonella adhesion is decreased by hypoxia due to adhesion and motility structure crosstalk.Veterinary research · 2023Article
- Anoxia Rapidly Induces Changes in Expression of a Large and Diverse Set of Genes in Endothelial Cells.International journal of molecular sciences · 2023Article
- HIF and MYC signaling in adrenal neoplasms of the neural crest: implications for pediatrics.Frontiers in endocrinology · 2023Review
- Hypoxia signaling in human health and diseases: implications and prospects for therapeutics.Signal transduction and targeted therapy · 2022Review
- Review
- Prolyl Hydroxylase Domain Protein Inhibitor Not Harboring a 2-Oxoglutarate Scaffold Protects against Hypoxic Stress.ACS pharmacology & translational science · 2022Article
- A novel mechanism for A-to-I RNA-edited AZIN1 in promoting tumor angiogenesis in colorectal cancer.Cell death & disease · 2022Article
- Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy.Cancers · 2022Review
- Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer.Scientific reports · 2021Article
- The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors-A Review of Literature.International journal of molecular sciences · 2021Review
- Key genes and drug delivery systems to improve the efficiency of chemotherapy.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Hypoxia as a Driving Force of Pluripotent Stem Cell Reprogramming and Differentiation to Endothelial Cells.Biomolecules · 2020Review
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Recently we have shown that hypoxia as well as overexpression of the stable form of hypoxia-inducible factor-1α (HIF-1α) diminished the expression of interleukin-8 (IL-8) by inhibition of the Nrf2 transcription factor in HMEC-1 cells. Because HIF isoforms may exert different effects, we aimed to examine the influence of HIF-2α on IL-8 expression in endothelial cells. In contrast to HIF-1α, overexpression of HIF-2α obtained by adenoviral transduction resulted in increased expression of IL-8 in an Nrf2-independent way. Importantly, HIF-2α augmented the activity of SP-1, a transcription factor involved in IL-8 regulation and known coactivator of c-Myc. Additionally, HIF-1 decreased, whereas HIF-2 increased, c-Myc expression, and silencing of Mxi-1, a c-Myc antagonist, restored IL-8 expression downregulated by HIF-1α or hypoxia. Accordingly, binding of c-Myc to the IL-8 promoter was abolished in hypoxia. Importantly, both severe (0.5% O(2)) and mild (5% O(2)) hypoxia diminished IL-8 expression despite the stabilization of both HIF-1 and HIF-2. This study reveals the opposite roles of HIF-1α and HIF-2α in the regulation of IL-8 expression in endothelial cells. However, despite stabilization of both isoforms in hypoxia the effect of HIF-1 is predominant, and downregulation of IL-8 expression in hypoxia is caused by attenuation of Nrf2 and c-Myc.
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