Vitamin D Receptor and Jak-STAT Signaling Crosstalk Results in Calcitriol-Mediated Increase of Hepatocellular Response to IFN-α.

Détails

ID Serval
serval:BIB_E3F6D43CC5E3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Vitamin D Receptor and Jak-STAT Signaling Crosstalk Results in Calcitriol-Mediated Increase of Hepatocellular Response to IFN-α.
Périodique
Journal of Immunology
Auteur(s)
Lange C.M., Gouttenoire J., Duong F.H., Morikawa K., Heim M.H., Moradpour D.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
192
Numéro
12
Pages
6037-6044
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
Recent clinical research suggests a role for vitamin D in the response to IFN-α-based therapy of chronic hepatitis C. Therefore, we aimed to explore the underlying mechanisms in vitro. Huh-7.5 cells harboring subgenomic hepatitis C virus (HCV) replicons or infected with cell culture-derived HCV were exposed to bioactive 1,25-dihydroxyvitamin D3 (calcitriol) with or without IFN-α. In these experiments, calcitriol alone had no effect on the HCV life cycle. However, calcitriol enhanced the inhibitory effect of IFN-α on HCV replication. This effect was based on a calcitriol-mediated increase of IFN-α-induced gene expression. Further mechanistic studies revealed a constitutive inhibitory interaction between the inactive vitamin D receptor (VDR) and Stat1, which was released upon stimulation with calcitriol and IFN-α. As a consequence, IFN-α-induced binding of phosphorylated Stat1 to its DNA target sequences was enhanced by calcitriol. Importantly, and in line with these observations, silencing of the VDR resulted in an enhanced hepatocellular response to IFN-α. Our findings identify the VDR as a novel suppressor of IFN-α-induced signaling through the Jak-STAT pathway.
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/07/2014 17:52
Dernière modification de la notice
20/08/2019 17:07
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