Impaired expression of hypoxia-inducible factor-1α in cystic fibrosis airway epithelial cells - a role for HIF-1 in the pathophysiology of CF?

J Cyst Fibros. 2011 Jul;10(4):286-90. doi: 10.1016/j.jcf.2011.02.005. Epub 2011 Mar 21.

Abstract

The continuous infection-inflammation cycle plays a crucial role in the progression of cystic fibrosis (CF) disease. This noxious loop can be aggravated by a reduced partial pressure of oxygen in the blood, hypoxemia, present in CF patients. These interconnected factors, hypoxia, inflammation and infection, by stabilizing the hypoxia-inducible factor-1α (HIF-1α) protein subunit, are able to activate the transcription factor HIF-1. To date, data investigating the potential role of HIF-1 in CF are scarce. Our results demonstrated that HIF-1α protein expression was altered in CF-affected compared to CFTR-corrected airway epithelial cells in unsimulated and simulated hypoxic conditions. In contrast, when CF-affected cells were infected with Pseudomonas aeruginosa, HIF-1α was more stabilized compared to CFTR-corrected cells. As HIF-1 is linked with an efficient immune response and pulmonary complications in cystic fibrosis, this difference in HIF-1α protein levels could have an impact in the CF pathology and the persistence of P. aeruginosa infection.

Publication types

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

MeSH terms

  • Bronchi / cytology
  • Cell Line
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis / microbiology
  • Cystic Fibrosis / physiopathology*
  • Humans
  • Hypoxia / metabolism
  • Hypoxia / physiopathology
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Pseudomonas Infections / metabolism
  • Pseudomonas Infections / physiopathology
  • Pseudomonas aeruginosa
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / metabolism*

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit