HIF-1α inhibition ameliorates an allergic airway disease via VEGF suppression in bronchial epithelium
- Authors
- Kim S.R.; Lee K.S.; Park H.S.; Park S.J.; Min K.H.; Moon H.; Puri K.D.; Lee Y.C.
- Issue Date
- Oct-2010
- Keywords
- Allergic airway disease; Hypoxia-inducible factor-1α; PI3K-δ; RNA interference; Vascular endothelial growth factor
- Citation
- European Journal of Immunology, v.40, no.10, pp 2858 - 2869
- Pages
- 12
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- European Journal of Immunology
- Volume
- 40
- Number
- 10
- Start Page
- 2858
- End Page
- 2869
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/15505
- DOI
- 10.1002/eji.200939948
- ISSN
- 0014-2980
1521-4141
- Abstract
- Hypoxia-inducible factor-1α (HIF-1α) plays a critical role in immune and inflammatory responses. One of the HIF-1α target genes is vascular endothelial growth factor (VEGF), which is a potent stimulator of inflammation, airway remodeling, and physiologic dysregulation in allergic airway diseases. Using OVA-treated mice and murine tracheal epithelial cells, the signaling networks involved in HIF-1α activation and the role of HIF-1α in the pathogenesis of allergic airway disease were investigated. Transfection of airway epithelial cells with HIF-1α siRNA suppressed VEGF expression. In addition, the increased levels of HIF-1α and VEGF in lung tissues after OVA inhalation were substantially decreased by an HIF-1α inhibitor, 2-methoxyestradiol. Our data also show that the increased numbers of inflammatory cells, increased airway hyperresponsiveness, levels of IL-4, IL-5, IL-13, and vascular permeability in the lungs after OVA inhalation were significantly reduced by 2-methoxyestradiol or a VEGF inhibitor, CBO-P11. Moreover, we found that inhibition of the PI3K p110d isoform (PI3K-δ) or HIF-1α reduced OVA-induced HIF-1α activation in airway epithelial cells. These findings indicate that HIF-1α inhibition may attenuate antigen-induced airway inflammation and hyperresponsiveness through the modulation of vascular leakage mediated by VEGF, and that PI3K-δ signaling may be involved in the allergen-induced HIF-1α activation. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.
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- Appears in
Collections - 2. Clinical Science > Department of Pulmonary, Allergy, and Critical Care Medicine > 1. Journal Articles
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