title: HIF-1α inhibition reduces nasal inflammation in a murine allergic rhinitis model.
abstract: BACKGROUND
  Hypoxia-inducible factor 1α (HIF-1α) is an important regulator of immune and inflammatory responses. We hypothesized that nasal allergic inflammation is attenuated by HIF-1α inhibition and strengthened by HIF-1α stabilization.
  
  
  OBJECTIVE
  To elucidate the role of HIF-1α in a murine model of allergic rhinitis (AR).
  
  
  METHODS
  Mice were pretreated with the HIF-1α inhibitor 2-methoxyestradiol (2ME2) or the HIF-1α inducer cobalt chloride (CoCl(2)) in an established AR murine model using ovalbumin (OVA)-sensitized BALB/c mice. HIF-1α and vascular endothelial growth factor (VEGF) expression in nasal mucosa was measured and multiple parameters of allergic responses were evaluated.
  
  
  RESULTS
  HIF-1α and VEGF levels were locally up-regulated in nasal mucosa during AR. Inflammatory responses to OVA challenge, including nasal symptoms, inflammatory cell infiltration, eosinophil recruitment, up-regulation of T-helper type 2 cytokines in nasal lavage fluid, and serum OVA-specific IgE levels were present in the OVA-challenged mice. 2ME2 effectively inhibited HIF-1α and VEGF expression and attenuated the inflammatory responses. Stabilization of HIF-1α by CoCl(2) facilitated nasal allergic inflammation. HIF-1α protein levels in nasal airways correlated with the severity of AR in mice.
  
  
  CONCLUSIONS
  HIF-1α is intimately involved in the pathogenesis of nasal allergies, and the inhibition of HIF-1α may be useful as a novel therapeutic approach for AR.
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhou
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Zhang
authors.forename: Lu-Ping
authors.initials: LP
authors.lastname: Zhu
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D003035:Cobalt / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007073:Immunoglobulin E / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology*; D010047:Ovalbumin / Q000378:metabolism; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016207:Cytokines; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D007073:Immunoglobulin E; D003035:Cobalt; D004958:Estradiol; D000077584:2-Methoxyestradiol; D010047:Ovalbumin; C018021:cobaltous chloride