About: Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression

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About: Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression
Creator	Chen, Limin Selzner, Nazia Ma, Xue-Zhong Khattar, Ramzi Cherepanov, Vera Selzner, Markus Mcgilvray, Ian Feld, Jordan Macparland, Sonya
source	PMC
abstract	Inflammation may be maladaptive to the control of viral infection when it impairs interferon (IFN) responses, enhancing viral replication and spread. Dysregulated immunity as a result of inappropriate innate inflammatory responses is a hallmark of chronic viral infections such as, hepatitis B virus and hepatitis C virus (HCV). Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Human hepatoma cells and primary murine hepatocytes were treated with TNF-α/LPS/IL-6/IL-10 and USP18, phosphorylated (p)-STAT1 and myxovirus (influenza virus) resistance 1 (Mx1) expression was determined. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. Liver inflammation was induced in vivo using a murine model of hepatic ischemia/reperfusion injury. Hepatic ischemia/reperfusion injury led to an induction of USP18 expression in liver tissue and promotion of lymphocytic choriomeningitis replication. These data demonstrate that certain inflammatory stimuli (TNF-α and LPS) but not others (IL-6 and IL-10) target USP18 expression and thus inhibit IFN signaling. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with USP18 representing a potential target for intervention in various inflammatory states. IMPORTANCE Inflammation may prevent the control of viral infection when it impairs the innate immune response, enhancing viral replication and spread. Blunted immunity as a result of inappropriate innate inflammatory responses is a common characteristic of chronic viral infections. Previous studies have shown that expression of certain interferon-stimulated genes is upregulated in chronic HCV infection, leading to impaired hepatocyte responses. In this study, we show that multiple inflammatory stimuli can modulate interferon stimulated gene expression and thus inhibit hepatocyte interferon signaling via USP18 induction. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with the induction of USP18 representing a potential target for intervention in various inflammatory states.
has issue date	2016-05-27(xsd:dateTime)
bibo:doi	10.1128/jvi.02557-15
bibo:pmid	27009955
has license	cc-by
sha1sum (hex)	75882d6856d4243248aa32fe119153efeb0dbe12
schema:url	https://doi.org/10.1128/jvi.02557-15
resource representing a document's title	Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression
has PubMed Central identifier	PMC4886784
has PubMed identifier	27009955
schema:publication	J Virol
resource representing a document's body	covid:75882d6856d4243248aa32fe119153efeb0dbe12#body_text
is schema:about of	named entity 'HEPATOCYTES' named entity 'interferon' named entity 'LIPOPOLYSACCHARIDE' named entity 'TUMOR NECROSIS FACTOR ALPHA ' named entity 'TUMOR NECROSIS FACTOR ALPHA ' named entity 'INCREASING' named entity 'LIPOPOLYSACCHARIDE' named entity 'VIROL' named entity 'HEPATOCYTES' named entity 'EXPRESSION' named entity 'INCREASING' named entity '90%' named entity 'CHEN' named entity 'PROTEASE' named entity 'LIKE' named entity 'PROTEASE' named entity 'INTERFERON SIGNALING' named entity 'CITATION' named entity 'FELD' named entity 'LIKE' named entity 'UBIQUITIN' named entity 'INTERFERON SIGNALING' named entity 'EXPRESSION' named entity 'UBIQUITIN' named entity 'signaling' named entity 'Citation' named entity 'ubiquitin-like' named entity 'USP18' named entity 'tumor necrosis factor alpha' named entity 'Ubiquitin-Like' named entity 'USP18' named entity 'HPRT' named entity 'USP18' named entity 'LPS' named entity 'negative-feedback' named entity 'penicillin' named entity 'ISG' named entity 'qPCR' named entity 'USP18' named entity 'pharmacologically' named entity 'USP18' named entity 'wild-type' named entity 'siRNA' named entity 'mice' named entity 'HCV' named entity 'USP18' named entity 'proinflammatory' named entity 'transfected' named entity 'proviral' named entity 'USP18' named entity 'ISGs' named entity 'hepatocyte' named entity 'LPS' named entity 'IL-23' named entity 'siRNA' named entity 'interferon-stimulated genes' named entity 'IL-10' named entity 'viral infection' named entity 'liver inflammation' named entity 'USP18' named entity 'infection' named entity 'cell line' named entity 'hepatocytes' named entity 'mice' named entity 'IFN' named entity 'hepatocytes' named entity 'RNA' named entity 'ISGs' named entity 'liver tissue' named entity 'regulatory pathway' named entity 'USP18' named entity 'LPS' named entity 'IFN'

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