Journal article

Publication year: 2005

Pages: 297-310

Journal: Journal of Interferon and Cytokine Research

Volume number: 25

Issue number: 6

ISSN: 1079-9907

DOI Link: https://doi.org/10.1089/jir.2005.25.297

Publisher: Mary Ann Liebert

Abstract: 
Hypoxia-inducible factor-1 (HIF-1) is a dimeric transcriptional complex that has been recognized primarily for its role in the maintenance of oxygen and energy homoeostasis. The HIF-1 alpha subunit is O-2 labile and is degraded by the proteasome following prolyl-hydroxylation and ubiquitination in normoxic cells. The present review summarizes evidence that HIF-1 is also involved in immune reactions. Immunomodulatory peptides, including interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), stimulate HIF-1 dependent gene expression even in normoxic cells. Both the hypoxic and the cytokine-induced activation of HIF-1 involve the phosphatidylinositol-3- kinase (PI3K) and the mitogen-activated protein kinase (MAPK) signaling pathways. In addition, heat shock proteins (HSP) and other cofactors interact with HIF-1 subunits. HIF-1 increases the transcription of several genes for proteins that promote blood flow and inflammation, including vascular endothelial growth factor (VEGF), heme oxygenase-1, endothelial and inducible nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2). The pharmacologic activation of the HIF-1 complex can be desirable in ischemic and inflammatory disorders. In contrast, HIF-1 blockade may be beneficial to prevent tumor angiogenesis and tumor growth.

Harvard Citation style: Hellwig-Bürgel, T., Stiehl, D., Wagner, A., Metzen, E. and Jelkmann, W. (2005) Hypoxia-inducible factor-1 (HIF-1): A novel transcription factor in immune reactions, Journal of Interferon and Cytokine Research, 25(6), pp. 297-310. https://doi.org/10.1089/jir.2005.25.297

APA Citation style: Hellwig-Bürgel, T., Stiehl, D., Wagner, A., Metzen, E., & Jelkmann, W. (2005). Hypoxia-inducible factor-1 (HIF-1): A novel transcription factor in immune reactions. Journal of Interferon and Cytokine Research. 25(6), 297-310. https://doi.org/10.1089/jir.2005.25.297