Abstract
BackgroundHypoxia-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.ObjectiveTo elucidate the role of HIF-1α in a murine model of allergic rhinitis (AR).MethodsMice were pretreated with the HIF-1α inhibitor 2-methoxyestradiol (2ME2) or the HIF-1α inducer cobalt chloride (CoCl2) 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.ResultsHIF-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 CoCl2 facilitated nasal allergic inflammation. HIF-1α protein levels in nasal airways correlated with the severity of AR in mice.ConclusionsHIF-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.
Highlights
Allergic rhinitis (AR) is a common inflammatory disease characterized by nasal itching, sneezing, rhinorrhea, and nasal congestion
Hypoxia-inducible factor 1a (HIF-1a) is intimately involved in the pathogenesis of nasal allergies, and the inhibition of HIF-1a may be useful as a novel therapeutic approach for AR
Allergic mice treated with 2ME2 showed marked reductions in the number of infiltrating eosinophils, while CoCl2 treatment enhanced eosinophil infiltration into the nasal mucosa
Summary
Allergic rhinitis (AR) is a common inflammatory disease characterized by nasal itching, sneezing, rhinorrhea, and nasal congestion. It is frequently associated with other inflammatory diseases such as asthma, rhinosinusitis, allergic conjunctivitis, otitis media with effusion, and adenoid hypertrophy [1]. Allergic inflammation in the nasal airways is mediated by T-helper type 2 (Th2) cells together with mast cells, B cells, and eosinophils, as well as a number of inflammatory cytokines and chemokines [2,3]. The hypoxia-inducible factor 1 (HIF1) transcription complex regulates the activation of different immune cells during the inflammatory response [4,5]. Hypoxia-inducible factor 1a (HIF-1a) is an important regulator of immune and inflammatory responses. We hypothesized that nasal allergic inflammation is attenuated by HIF-1a inhibition and strengthened by HIF-1a stabilization
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
