| First Author | Greenwood KK | Year | 2012 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 302 |
| Issue | 5 | Pages | L455-62 |
| PubMed ID | 22180657 | Mgi Jnum | J:183445 |
| Mgi Id | MGI:5318672 | Doi | 10.1152/ajplung.00193.2011 |
| Citation | Greenwood KK, et al. (2012) Neonatal epithelial hypoxia inducible factor-1alpha expression regulates the response of the lung to experimental asthma. Am J Physiol Lung Cell Mol Physiol 302(5):L455-62 |
| abstractText | Allergic airway disease is characterized by a T helper type 2 cell-mediated airway inflammation and airway hyperresponsiveness. Little is known about the role of hypoxia-mediated signaling in the progression of the disease. To address this knowledge gap, a mouse model was created in which doxycycline exposure induces the functional deletion of hypoxia inducible factor-1alpha from alveolar type II and Clara cells of the lung. When hypoxia inducible factor-1alpha deletion was induced during the early postnatal development period of the lung, the mice displayed an enhanced response to the ovalbumin model of allergic airway disease. These hypoxia inducible factor-1alpha-deficient mice exhibit increased cellular infiltrates, eosinophilia in the lavage fluid and parenchyma, and T helper type 2 cytokines, as compared with ovalbumin-treated control mice. Moreover, these hypoxia inducible factor-1alpha-deficient mice display increased airway resistance when compared with their control counterparts. Interestingly, if the loss of hypoxia inducible factor-1alpha was induced in early adulthood, the exacerbated phenotype was not observed. Taken together, these results suggest that epithelial hypoxia inducible factor-1alpha plays an important role in establishing the innate immunity of the lung and epithelial-specific deficiency in the transcription factor, during early postnatal development, increases the severity of inflammation and functional airway resistance, following ovalbumin challenge. Finally, these results might explain some of the chronic respiratory pathology observed in premature infants, especially those that receive supplemental oxygen. This early hyperoxic exposure, from normal ambient and supplemental oxygen, would presumably inhibit normal hypoxia inducible factor-1alpha signaling, mimicking the functional deletion described. |
