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Pegylated IFN-α regulates hepatic gene expression through transient Jak/STAT activation

Pegylated IFN-α regulates hepatic gene expression through transient Jak/STAT activation

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DILL, Michael T., Zuzanna MAKOWSKA, Gaia TRINCUCCI, Andreas J. GRUBER, Julia E. VOGT, Magdalena FILIPOWICZ, Diego CALABRESE, Ilona KROL, Daryl T. LAU, Luigi TERRACCIANO, 2014. Pegylated IFN-α regulates hepatic gene expression through transient Jak/STAT activation. In: The Journal of clinical investigation. American Society for Clinical Investigation. 124(4), pp. 1568-1581. ISSN 0021-9738. eISSN 1558-8238. Available under: doi: 10.1172/JCI70408

@article{Dill2014-04Pegyl-51055, title={Pegylated IFN-α regulates hepatic gene expression through transient Jak/STAT activation}, year={2014}, doi={10.1172/JCI70408}, number={4}, volume={124}, issn={0021-9738}, journal={The Journal of clinical investigation}, pages={1568--1581}, author={Dill, Michael T. and Makowska, Zuzanna and Trincucci, Gaia and Gruber, Andreas J. and Vogt, Julia E. and Filipowicz, Magdalena and Calabrese, Diego and Krol, Ilona and Lau, Daryl T. and Terracciano, Luigi} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/51055"> <dcterms:issued>2014-04</dcterms:issued> <dc:creator>Calabrese, Diego</dc:creator> <dc:contributor>Terracciano, Luigi</dc:contributor> <dc:creator>Makowska, Zuzanna</dc:creator> <dc:creator>Lau, Daryl T.</dc:creator> <dc:contributor>Vogt, Julia E.</dc:contributor> <dc:creator>Gruber, Andreas J.</dc:creator> <dc:creator>Terracciano, Luigi</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/51055"/> <dc:rights>terms-of-use</dc:rights> <dcterms:abstract xml:lang="eng">The use of pegylated interferon-α (pegIFN-α) has replaced unmodified recombinant IFN-α for the treatment of chronic viral hepatitis. While the superior antiviral efficacy of pegIFN-α is generally attributed to improved pharmacokinetic properties, the pharmacodynamic effects of pegIFN-α in the liver have not been studied. Here, we analyzed pegIFN-α-induced signaling and gene regulation in paired liver biopsies obtained prior to treatment and during the first week following pegIFN-α injection in 18 patients with chronic hepatitis C. Despite sustained high concentrations of pegIFN-α in serum, the Jak/STAT pathway was activated in hepatocytes only on the first day after pegIFN-α administration. Evaluation of liver biopsies revealed that pegIFN-α induces hundreds of genes that can be classified into four clusters based on different temporal expression profiles. In all clusters, gene transcription was mainly driven by IFN-stimulated gene factor 3 (ISGF3). Compared with conventional IFN-α therapy, pegIFN-α induced a broader spectrum of gene expression, including many genes involved in cellular immunity. IFN-induced secondary transcription factors did not result in additional waves of gene expression. Our data indicate that the superior antiviral efficacy of pegIFN-α is not the result of prolonged Jak/STAT pathway activation in hepatocytes, but rather is due to induction of additional genes that are involved in cellular immune responses.</dcterms:abstract> <dc:contributor>Krol, Ilona</dc:contributor> <dc:language>eng</dc:language> <dc:contributor>Makowska, Zuzanna</dc:contributor> <dc:contributor>Lau, Daryl T.</dc:contributor> <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/> <dc:creator>Trincucci, Gaia</dc:creator> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2020-09-28T10:18:11Z</dcterms:available> <dcterms:title>Pegylated IFN-α regulates hepatic gene expression through transient Jak/STAT activation</dcterms:title> <dc:contributor>Dill, Michael T.</dc:contributor> <dc:contributor>Filipowicz, Magdalena</dc:contributor> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Trincucci, Gaia</dc:contributor> <dc:contributor>Calabrese, Diego</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2020-09-28T10:18:11Z</dc:date> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:creator>Dill, Michael T.</dc:creator> <dc:creator>Filipowicz, Magdalena</dc:creator> <dc:contributor>Gruber, Andreas J.</dc:contributor> <dc:creator>Vogt, Julia E.</dc:creator> <dc:creator>Krol, Ilona</dc:creator> </rdf:Description> </rdf:RDF>

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