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

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-1 alpha (HIF-1 alpha) 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-1 alpha 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-1 alpha. 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-1 alpha protein levels could have an impact in the CF pathology and the persistence of P. aeruginosa infection. (C) 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.