The role of hypoxia-inducible factor 1α in allergic rhinitis.
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.


CONCLUSIONS
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.
Department of Otorhinolaryngology, Dankook University College of Medicine, Cheonan, South Korea.
Ji-Hun
JH
Mo
Ji-Hye
JH
Kim
Dae Jun
DJ
Lim
Eun Hee
EH
Kim
D000077584:2-Methoxyestradiol; D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007073:Immunoglobulin E / Q000378:metabolism; D007274:Injections, Intraperitoneal; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000187:drug effects / Q000473:pathology*; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D065631:Rhinitis, Allergic / Q000276:immunology*; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D000485:Allergens; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015848:Interleukin-5; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D015847:Interleukin-4; D007073:Immunoglobulin E; D004958:Estradiol; D000077584:2-Methoxyestradiol; D010047:Ovalbumin