| First Author | Zhou H | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 11 | Pages | e48618 |
| PubMed ID | 23133644 | Mgi Jnum | J:194695 |
| Mgi Id | MGI:5474526 | Doi | 10.1371/journal.pone.0048618 |
| Citation | Zhou H, et al. (2012) HIF-1alpha inhibition reduces nasal inflammation in a murine allergic rhinitis model. PLoS One 7(11):e48618 |
| abstractText | BACKGROUND: Hypoxia-inducible factor 1alpha (HIF-1alpha) is an important regulator of immune and inflammatory responses. We hypothesized that nasal allergic inflammation is attenuated by HIF-1alpha inhibition and strengthened by HIF-1alpha stabilization. OBJECTIVE: To elucidate the role of HIF-1alpha in a murine model of allergic rhinitis (AR). METHODS: Mice were pretreated with the HIF-1alpha inhibitor 2-methoxyestradiol (2ME2) or the HIF-1alpha inducer cobalt chloride (CoCl(2)) in an established AR murine model using ovalbumin (OVA)-sensitized BALB/c mice. HIF-1alpha and vascular endothelial growth factor (VEGF) expression in nasal mucosa was measured and multiple parameters of allergic responses were evaluated. RESULTS: HIF-1alpha 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-1alpha and VEGF expression and attenuated the inflammatory responses. Stabilization of HIF-1alpha by CoCl(2) facilitated nasal allergic inflammation. HIF-1alpha protein levels in nasal airways correlated with the severity of AR in mice. CONCLUSIONS: HIF-1alpha is intimately involved in the pathogenesis of nasal allergies, and the inhibition of HIF-1alpha may be useful as a novel therapeutic approach for AR. |
