NDLI: Vitamin D receptor and Jak-STAT signaling crosstalk results in calcitriol-mediated increase of hepatocellular response to IFN- .

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Duong, François H. T. Heim, Markus H. Gouttenoire, Jérôme Moradpour, Darius Lange, Christian M. Morikawa, Kenichi
Description	Author Affiliation: Lange CM ( Division of Gastroenterology and Hepatology, Vaud University Hospital Center, University of Lausanne, CH-1011 Lausanne, Switzerland); Gouttenoire J ( Division of Gastroenterology and Hepatology, Vaud University Hospital Center, University of Lausanne, CH-1011 Lausanne, Switzerland); Duong FH ( Department of Biomedicine, University Hospital Basel, CH-4031 Basel, Switzerland.); Morikawa K ( Division of Gastroenterology and Hepatology, Vaud University Hospital Center, University of Lausanne, CH-1011 Lausanne, Switzerland); Heim MH ( Department of Biomedicine, University Hospital Basel, CH-4031 Basel, Switzerland.); Moradpour D ( Division of Gastroenterology and Hepatology, Vaud University Hospital Center, University of Lausanne, CH-1011 Lausanne, Switzerland)
Abstract	Recent clinical research suggests a role for vitamin D in the response to IFN- -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- . In these experiments, calcitriol alone had no effect on the HCV life cycle. However, calcitriol enhanced the inhibitory effect of IFN- on HCV replication. This effect was based on a calcitriol-mediated increase of IFN- -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- . As a consequence, IFN- -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- . Our findings identify the VDR as a novel suppressor of IFN- -induced signaling through the Jak-STAT pathway.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	12
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Hepacivirus Physiology Hepatitis C Immunology Interferon-alpha Pharmacology Janus Kinases Receptors, Calcitriol Stat1 Transcription Factor Signal Transduction Virus Replication Calcitriol Cell Line Gene Expression Regulation Drug Effects Genetics Drug Therapy Pathology Phosphorylation Vitamins Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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