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https://hdl.handle.net/2440/90841
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dc.contributor.author | Tse, E. | - |
dc.contributor.author | Helbig, K. | - |
dc.contributor.author | Van der Hoek, K. | - |
dc.contributor.author | McCartney, E. | - |
dc.contributor.author | Van der Hoek, M. | - |
dc.contributor.author | George, J. | - |
dc.contributor.author | Beard, M. | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Journal of Interferon and Cytokine Research, 2015; 35(5):392-400 | - |
dc.identifier.issn | 1079-9907 | - |
dc.identifier.issn | 1557-7465 | - |
dc.identifier.uri | http://hdl.handle.net/2440/90841 | - |
dc.description | Online Ahead of Print: January 14, 2015 | - |
dc.description.abstract | The pathogenesis of nonalcoholic steatohepatitis is primarily an immune-driven disease and a known factor associated with treatment failure of chronic hepatitis C with interferon (IFN) and ribavirin. We studied the hepatocyte response in a model of steatosis at the transcriptome level and the antiviral action of IFN against hepatitis C virus (HCV) in this setting. In this study, we have shown that lipid loading (oleic acid and palmitic acid, OA:PA) of Huh-7 cells leads to increased expression of classical interferon-stimulated genes (ISGs) and NF-κβ-dependent pro-inflammatory genes. A selective blocker of Toll-like receptor (TLR)2 signaling suppressed NF-κβ promoter activity by OA:PA, suggesting that free fatty acids (FFAs) act as a TLR2 pathogen-associated molecular pattern. Furthermore, in the presence of OA:PA, IFN stimulation and HCV infection (Jc1) increased ISG expression. Somewhat counterintuitive to the increase in ISGs, the anti-HCV activity of IFN was attenuated in the presence of OA:PA. Interestingly, the combination of OA:PA, HCV, and IFN-α stimulation resulted in a significant increase in CXCL8 protein production, a cytokine known to have anti-IFN modulating activity. Thus, in an in vitro model of steatosis, the FFAs OA and PA drive an NF-κβ-dependent inflammatory and ISG gene expression profile via TLR2 activation. Furthermore, FFA synergistically increases IFN-driven gene expression that may account for HCV treatment failure in vivo. | - |
dc.description.statementofresponsibility | Edmund Tse, Karla J. Helbig, Kylie Van der Hoek, Erin M. McCartney, Mark Van der Hoek, Jacob George, and Michael R. Beard | - |
dc.language.iso | en | - |
dc.publisher | Mary Ann Liebert | - |
dc.rights | © Mary Ann Liebert, Inc. | - |
dc.source.uri | http://dx.doi.org/10.1089/jir.2014.0165 | - |
dc.subject | Cell Line | - |
dc.subject | Humans | - |
dc.subject | Hepacivirus | - |
dc.subject | Hepatitis C, Chronic | - |
dc.subject | Fatty Liver | - |
dc.subject | Fatty Acids | - |
dc.subject | Oleic Acid | - |
dc.subject | Palmitic Acid | - |
dc.subject | NF-kappa B | - |
dc.subject | Interferons | - |
dc.subject | Cluster Analysis | - |
dc.subject | Gene Expression Profiling | - |
dc.subject | Virus Replication | - |
dc.subject | Gene Expression Regulation | - |
dc.subject | Drug Synergism | - |
dc.subject | Toll-Like Receptor 2 | - |
dc.subject | Transcriptome | - |
dc.title | Fatty acids induce a pro-inflammatory gene expression profile in Huh-7 cells that attenuates the anti-HCV action of interferon | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1089/jir.2014.0165 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/510448 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Van der Hoek, K. [0000-0002-7904-7340] | - |
dc.identifier.orcid | Beard, M. [0000-0002-4106-1016] | - |
Appears in Collections: | Aurora harvest 7 Molecular and Biomedical Science publications |
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