RSV causes HIF-1alpha stabilization via NO release in primary bronchial epithelial cells.
RSV infection is characterized by airway edema. Stabilization of hypoxia inducible factor-1alpha (HIF-1alpha) is important in both inflammation and edema formation. In this study we evaluated whether RSV induced release of nitric oxide (NO) by bronchial airway epithelial cells leading to the stabilization of HIF-1alpha and subsequent transcription of VEGF(165). Primary human bronchial epithelial cells (HBEpC) were used; cell supernatants were analyzed. Western blot analysis was used for the detection of HIF-1alpha. Bronchial airway epithelial monolayer permeability was assessed using electric cell-substrate impedance sensing (ECIS) in real time. There was increased stabilization of HIF-1alpha in RSV infected cells. Addition of an NO inhibitor blocked RSV mediated HIF-1alpha expression. Antagonism of NO also inhibited VEGF production and HBEpC monolayer permeability. Our results demonstrate that in HBEpC, RSV induced NO causes stabilization of HIF-1alpha in vitro.
Kilani
Muna M
MM
Indiana University Medical Center, Indianapolis, USA.
Mohammed
Kamal A
KA
Nasreen
Najmunnisa
N
Tepper
Robert S
RS
Antony
Veena B
VB
D001565:Benzoates / Q000494:pharmacology; D001980:Bronchi / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D017097:Electric Impedance; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007093:Imidazoles / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism*; D010539:Permeability; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity*; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism
D001565:Benzoates; D004268:DNA-Binding Proteins; D016166:Free Radical Scavengers; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007093:Imidazoles; D009687:Nuclear Proteins; D014157:Transcription Factors; D042442:Vascular Endothelial Growth Factors; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009569:Nitric Oxide