The Role of Hypoxia-Inducible Factor 1α in Allergic Rhinitis. Issue 2 (March 2014)

• Record Type: Journal Article
• Authors: Mo, Ji-Hun; Kim, Ji-Hye; Lim, Dae Jun; Kim, Eun Hee
• Is Part Of: American journal of rhinology & allergy. Volume 28:Issue 2(2014)
• Page Start: e100
• Page End: e106
• Publication Date: 2014-03
• Subjects: Nose -- Periodicals; Allergy -- Periodicals; 616.21005
• DOI: 10.2500/ajra.2014.28.4025
• Languages: English
• ISSNs: 1945-8924

Abstract

Background: Hypoxia-inducible factor (HIF) 1alpha is expressed under hypoxic conditions and plays an important role in immune and inflammatory responses. The role of HIF-1alpha in allergic airways has been investigated mainly in bronchial asthma. This study investigated the role of HIF-1alpha in mouse models and patients with allergic rhinitis (AR). Methods: Balb/c mice were sensitized with ovalbumin (OVA) and alum and were challenged intranasally with OVA. The HIF-1alpha inhibitor, 2-methoxyestradiol (2-ME), was administered intraperitoneally and multiple parameters of allergic responses were evaluated. HIF-1alpha and vascular endothelial growth factor (VEGF) mRNA and protein expression were also evaluated in patients with AR and a correlation analysis between mRNA expression and allergic symptoms was performed. Results: In mouse models, the HIF-1alpha inhibitor 2-ME reduced allergic symptoms and eosinophilic infiltration into the nasal mucosa. 2-ME was found to suppress IgE production and inhibit local Th2 cytokine transcription in the nasal mucosa and systemic Th2 cytokine production by splenocytes. 2-ME also decreased HIF-1 and VEGF expression in nasal mucosa. An increase in HIF-1alpha and VEGF expression in the nasal mucosa of patients with AR was also observed. Conclusion: Our data suggest that HIF-1alpha plays an important role in mouse models and patients with AR. HIF-1alpha inhibitors induce antiallergic effects by decreasing both local and systemic Th2 cytokine (IL-4 and IL-5) production, IgE production, and eosinophil infiltration into the nasal mucosa in an AR model. HIF-1alpha and VEGF expression increased in the nasal mucosa of patients with AR, showing the role of HIF-1alpha in disease pathogenesis.