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Updated: Jun 21, 2026

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
Interferon-gamma induces prolyl hydroxylase (PHD)3 through a STAT1-dependent mechanism in human endothelial cells
Scott A Gerber1, Bogdan Yatsula, Cheryl L Maier
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520-8089 , USA.
Objective:
We previously reported that interferons (IFNs) regulate transcription of HIF-1alpha in human endothelial cells (ECs), linking immunity and hypoxia. Prolyl hydroxylases (PHDs) regulate expression of HIF-1alpha in response to hypoxia. We examined whether IFNs affect PHD expression and whether PHDs regulate the EC response to IFNs.
Methods And Results:
Human cell cultures were treated with various cytokines, and PHD expression was examined using qRT-PCR and immunoblotting. IFNgamma and, to a lesser extent, IFNalpha significantly induced PHD3, but not PHD1 or 2, mRNA, and protein expression selectively in ECs directly via a JAK/STAT1 pathway as demonstrated by pharmacological inhibition, siRNA knockdown, and chromatin immunoprecipitation. Inhibition of PHD activity with dimethyloxallyl glycine or desferroxamine reduced IFNg-dependent responses in these same cells.
Conclusions:
IFNgamma induces PHD3 through a JAK/STAT1-dependent mechanism in human ECs. Induction is independent of HIF-1alpha and may contribute to expression of IFNgamma-dependent genes.
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