title: Hypoxia inducible factor promotes murine allergic airway inflammation and is increased in asthma and rhinitis.
abstract: BACKGROUND
  New therapies are necessary to address inadequate asthma control in many patients. This study sets out to investigate whether hypoxia-inducible factor (HIF) is essential for development of allergic airway inflammation (AAI) and therefore a potential novel target for asthma treatment.
  
  
  METHODS
  Mice conditionally knocked out for HIF-1β were examined for their ability to mount an allergic inflammatory response in the lung after intratracheal exposure to ovalbumin. The effects of treating wild-type mice with either ethyl-3,4-dihydroxybenzoate (EDHB) or 2-methoxyestradiol (2ME), which upregulate and downregulate HIF, respectively, were determined. HIF-1α levels were also measured in endobronchial biopsies and bronchial fluid of patients with asthma and nasal fluid of patients with rhinitis after challenge.
  
  
  RESULTS
  Deletion of HIF-1β resulted in diminished AAI and diminished production of ovalbumin-specific IgE and IgG(1) . EDHB enhanced the inflammatory response, which was muted upon simultaneous inhibition of vascular endothelial growth factor (VEGF). EDHB and 2ME antagonized each other with regard to their effects on airway inflammation and mucus production. The levels of HIF-1α and VEGF increased in lung tissue and bronchial fluid of patients with asthma and in the nasal fluid of patients with rhinitis after challenge.
  
  
  CONCLUSIONS
  Our results support the notion that HIF is directly involved in the development of AAI. Most importantly, we demonstrate for the first time that HIF-1α is increased after challenge in patients with asthma and rhinitis. Therefore, we propose that HIF may be a potential therapeutic target for asthma and possibly for other inflammatory diseases.
authors.affiliation: Unidad de Investigacion En enfermedades Oncologicas, Hospital Infantil de Mexico, Federico Gomez, Mexico City, Mexico.
authors.forename: S
authors.initials: S
authors.lastname: Huerta-Yepez
authors.forename: G J
authors.initials: GJ
authors.lastname: Baay-Guzman
authors.forename: I G
authors.initials: IG
authors.lastname: Bebenek
authors.forename: R
authors.initials: R
authors.lastname: Hernandez-Pando
authors.forename: M I
authors.initials: MI
authors.lastname: Vega
authors.forename: L
authors.initials: L
authors.lastname: Chi
authors.forename: M
authors.initials: M
authors.lastname: Riedl
authors.forename: D
authors.initials: D
authors.lastname: Diaz-Sanchez
authors.forename: E
authors.initials: E
authors.lastname: Kleerup
authors.forename: D P
authors.initials: DP
authors.lastname: Tashkin
authors.forename: F J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: B
authors.initials: B
authors.lastname: Bonavida
authors.forename: M
authors.initials: M
authors.lastname: Zeidler
authors.forename: Oliver
authors.initials: O
authors.lastname: Hankinson
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D012220:Rhinitis / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000485:Allergens; D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010047:Ovalbumin; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C497443:Hif1a protein, mouse