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

Details

Serval ID
serval:BIB_E3F6D43CC5E3
Type
Article: article from journal or magazin.
Collection
Publications
Title
Vitamin D Receptor and Jak-STAT Signaling Crosstalk Results in Calcitriol-Mediated Increase of Hepatocellular Response to IFN-α.
Journal
Journal of Immunology
Author(s)
Lange C.M., Gouttenoire J., Duong F.H., Morikawa K., Heim M.H., Moradpour D.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
192
Number
12
Pages
6037-6044
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
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
Yes
Create date
11/07/2014 17:52
Last modification date
20/08/2019 17:07
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