Abstract
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). 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. 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. 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.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
