Format:
Online-Ressource
ISSN:
1521-4141
Content:
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 p110δ 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.
In:
volume:40
In:
number:10
In:
year:2010
In:
pages:2858-2869
In:
extent:13
In:
European journal of immunology, Weinheim : Wiley-VCH, 1971-, 40, Heft 10 (2010), 2858-2869 (gesamt 13), 1521-4141
Language:
English
DOI:
10.1002/eji.200939948
URN:
urn:nbn:de:101:1-2023042506335735245131
URL:
https://doi.org/10.1002/eji.200939948
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2023042506335735245131
URL:
https://d-nb.info/1286912296/34
URL:
https://doi.org/10.1002/eji.200939948
Bookmarklink