Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/90841
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Fatty acids induce a pro-inflammatory gene expression profile in Huh-7 cells that attenuates the anti-HCV action of interferon |
Author: | Tse, E. Helbig, K. Van der Hoek, K. McCartney, E. Van der Hoek, M. George, J. Beard, M. |
Citation: | Journal of Interferon and Cytokine Research, 2015; 35(5):392-400 |
Publisher: | Mary Ann Liebert |
Issue Date: | 2015 |
ISSN: | 1079-9907 1557-7465 |
Statement of Responsibility: | Edmund Tse, Karla J. Helbig, Kylie Van der Hoek, Erin M. McCartney, Mark Van der Hoek, Jacob George, and Michael R. Beard |
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. |
Keywords: | Cell Line Humans Hepacivirus Hepatitis C, Chronic Fatty Liver Fatty Acids Oleic Acid Palmitic Acid NF-kappa B Interferons Cluster Analysis Gene Expression Profiling Virus Replication Gene Expression Regulation Drug Synergism Toll-Like Receptor 2 Transcriptome |
Description: | Online Ahead of Print: January 14, 2015 |
Rights: | © Mary Ann Liebert, Inc. |
DOI: | 10.1089/jir.2014.0165 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/510448 |
Published version: | http://dx.doi.org/10.1089/jir.2014.0165 |
Appears in Collections: | Aurora harvest 7 Molecular and Biomedical Science publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.