Hypoxia: an alarm signal during intestinal inflammation

We review the signaling pathways involved and define how hypoxia may serve as an endogenous alarm signal for mucosal inflammatory disease

Sean P. Colgan; Cormac T. Taylor

2010

Scholarcy highlights

  • The intestinal epithelium lines the entire gastrointestinal tract, covering a surface area of approximately 300 m2 in the adult human and forming an essential barrier to the outside world
  • The oxygen-dependent regulatory role of PHDs may not be restricted to the hypoxiainducible factor pathway and may provide a means to better understand how hypoxia contributes to other aspects of inflammation
  • We have outlined the evidence for hypoxia as an important alarm signal within the intestinal mucosa
  • Studies derived from cultured cell systems, animal models and patient-derived materials have documented the that hypoxia is a significant component of the inflammatory microenvironment
  • It is notable that the increased susceptibility to colitis following the genetic deletion of intestinal epithelial HIF may be somewhat model-dependent and will require additional validatation with PHD inhibitors before clinical studies can be implements
  • HIF-1 and HIF-2 stabilization have been significantly associated with a number of cancers
  • Ongoing studies to define the differences and similarities between innate and adaptive immune responses will continue to teach us important lessons about the complexity of the gastrointestinal tract
  • Such information will provide new insight into the pathogenesis disease and importantly, will provide new targets as templates for the development of therapies for human disease

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