title: Impaired expression of hypoxia-inducible factor-1α in cystic fibrosis airway epithelial cells - a role for HIF-1 in the pathophysiology of CF?
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.
authors.affiliation: BIOMERIT Research Centre, Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Claire
authors.initials: C
authors.lastname: Legendre
authors.forename: Marlies J
authors.initials: MJ
authors.lastname: Mooij
authors.forename: Claire
authors.initials: C
authors.lastname: Adams
authors.forename: Fergal
authors.initials: F
authors.lastname: O'Gara
mesh_terms: D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000378:metabolism / Q000503:physiopathology; D011550:Pseudomonas aeruginosa; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit