Review: hypoxia-inducible factor-1 (HIF-1): a novel transcription factor in immune reactions

J Interferon Cytokine Res. 2005 Jun;25(6):297-310. doi: 10.1089/jir.2005.25.297.


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-1alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytokines / immunology
  • DNA-Binding Proteins / immunology*
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MAP Kinase Signaling System / immunology
  • Nuclear Proteins / immunology*
  • Proteasome Endopeptidase Complex / immunology
  • Transcription Factors / immunology*


  • Cytokines
  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Transcription Factors
  • Proteasome Endopeptidase Complex