Hypoxia, the HIF pathway and neutrophilic inflammatory responses

A. A. Roger Thompson, John Binham, Tracie Plant, Moira K. B. Whyte, Sarah R. Walmsley*

*Corresponding author for this work

Research output: Contribution to journalLiterature reviewpeer-review

Abstract

Many inflammatory diseases are characterised by persistent and inappropriate neutrophil activation, systemic or localised hypoxia, and bacterial colonisation. Hypoxia represents an important regulator of inflammatory responses because it inhibits neutrophil apoptosis, a process central to the timely resolution of inflammation. Progress in understanding how cells respond to hypoxia has led to the identification of hypoxia-inducible transcription factors (HIFs) and their hydroxylation by the prolyl hydroxylase enzymes. There is now a significant body of data to support a critical role for this HIF pathway in regulating neutrophil function. Moreover, manipulations of specific components of this pathway have very divergent effects on myeloid cell function. In this review, we will discuss the role individual members of the HIF pathway play in regulating key neutrophil functions and the implications this has for the development of effective therapeutic strategies that selectively target inappropriate neutrophil persistence while maintaining a fully competent immune response.

Original languageEnglish
Pages (from-to)471-477
Number of pages7
JournalBiological Chemistry
Volume394
Issue number4
DOIs
Publication statusPublished - Apr 2013

Keywords

  • innate immunity
  • myeloid cell
  • oxygen sensing
  • prolyl hydroxylase domain-containing enzymes (PHDs)
  • NF-KAPPA-B
  • INDUCIBLE-FACTOR
  • OXYGEN SENSOR
  • APOPTOSIS
  • HIF-1-ALPHA
  • ACTIVATION
  • RESOLUTION
  • MIGRATION
  • SEPSIS
  • PHD3

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