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Blood, Vol. 94 No. 5 (September 1), 1999:
pp. 1561-1567
Interleukin-1 and Tumor Necrosis Factor- Stimulate DNA Binding of
Hypoxia-Inducible Factor-1
Thomas Hellwig-Bürgel,
Karen Rutkowski,
Eric Metzen,
Joachim Fandrey, and
Wolfgang Jelkmann
From the Institut für Physiologie,
Medizinische Universität zu Lübeck,
Lübeck, Germany.
The rate of transcription of several genes encoding proteins
involved in O2 and energy homeostasis is controlled by
hypoxia-inducible factor-1 (HIF-1), a heterodimeric DNA binding complex
composed of  and  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-1 (IL-1)
and tumor necrosis factor- (TNF-), while no such effect has been
reported with respect to the VEGF gene, we investigated the effects of IL-1 and TNF- on the activation of the HIF-1 DNA-binding complex and the amount of HIF-1 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-1
increased HIF-1 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-1 nor TNF- decreased VEGF production.
The mRNA levels of HIF-1 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.
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J. J. Zulueta, R. Sawhney, U. Kayyali, M. Fogel, C. Donaldson, H. Huang, J. J. Lanzillo, and P. M. Hassoun
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J. E. Albina, B. Mastrofrancesco, J. A. Vessella, C. A. Louis, W. L. Henry Jr., and J. S. Reichner
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Am J Physiol Cell Physiol,
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D. M. STROKA, T. BURKHARDT, I. DESBAILLETS, R. H. WENGER, D. A. H. NEIL, C. BAUER, M. GASSMANN, and D. CANDINAS
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FASEB J,
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K. B. Sandau, J. Zhou, T. Kietzmann, and B. Brune
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J. Qian, K. Ramroop, A. McLeod, P. Bandari, D. H. Livingston, J. S. Harrison, and P. Rameshwar
Induction of Hypoxia-Inducible Factor-1{alpha} and Activation of Caspase-3 in Hypoxia-Reoxygenated Bone Marrow Stroma Is Negatively Regulated by the Delayed Production of Substance P
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L. Tacchini, P. Dansi, E. Matteucci, and M. A. Desiderio
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Carcinogenesis,
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J. J. E. Haddad, B. Safieh-Garabedian, N. E. Saadé, and S. C. Land
Thiol Regulation of Pro-Inflammatory Cytokines Reveals a Novel Immunopharmacological Potential of Glutathione in the Alveolar Epithelium
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R. Bos, H. Zhong, C. F. Hanrahan, E. C. M. Mommers, G. L. Semenza, H. M. Pinedo, M. D. Abeloff, J. W. Simons, P. J. van Diest, and E. van der Wall
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J Natl Cancer Inst,
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K. B. Sandau, J. Fandrey, and B. Brune
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Blood,
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J.-S. Silvestre, Z. Mallat, M. Duriez, R. Tamarat, M. F. Bureau, D. Scherman, N. Duverger, D. Branellec, A. Tedgui, and B. I. Levy
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Circ. Res.,
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A. Sodhi, S. Montaner, V. Patel, M. Zohar, C. Bais, E. A. Mesri, and J. S. Gutkind
The Kaposi's Sarcoma-associated Herpes Virus G Protein-coupled Receptor Up-Regulates Vascular Endothelial Growth Factor Expression and Secretion through Mitogen-activated Protein Kinase and p38 Pathways Acting on Hypoxia-inducible Factor 1{{alpha}}
Cancer Res.,
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R. M. Wanner, P. Spielmann, D. M. Stroka, G. Camenisch, I. Camenisch, A. Scheid, D. R. Houck, C. Bauer, M. Gassmann, and R. H. Wenger
Epolones induce erythropoietin expression via hypoxia-inducible factor-1alpha activation
Blood,
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R. Wenger
Mammalian oxygen sensing, signalling and gene regulation
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