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https://hdl.handle.net/2440/9497
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Type: | Journal article |
Title: | Expression of the CXCR3 ligand I-TAC by hepatocytes in chronic hepatitis C and its correlation with hepatic inflammation |
Author: | Helbig, K. Ruszkiewicz, A. Semendric, L. Harley, H. McColl, S. Beard, M. |
Citation: | Hepatology, 2004; 39(5):1220-1229 |
Publisher: | John Wiley & Sons Inc |
Issue Date: | 2004 |
ISSN: | 0270-9139 1527-3350 |
Statement of Responsibility: | Karla J. Helbig, Andrew Ruszkiewicz, Ljiljana Semendric, Hugh A.J. Harley, Shaun R. McColl, Michael R. Beard |
Abstract: | The factors that regulate lymphocyte traffic in chronic hepatitis C (CHC) are not completely defined. Interferon (IFN)-inducible T cell chemoattractant (I-TAC) is a relatively new member of the CXCR3 chemokine ligand family that selectively recruits activated T cells to sites of inflammation. To determine if I-TAC plays a role in CHC, we investigated I-TAC expression in hepatitis C virus (HCV)-infected liver biopsy material. I-TAC messenger RNA (mRNA) levels were significantly increased in HCV-infected liver compared with normal liver, which correlated with both portal and lobular inflammation. I-TAC expression was localized to hepatocytes throughout the liver lobule, with those in close proximity to active areas of inflammation expressing the highest concentration of I-TAC. In vitro, I-TAC mRNA and protein expression was inducible in Huh-7 cells following either IFN- or - stimulation and synergistically with tumor necrosis factor (TNF)-. Furthermore, transfection of Huh-7 cells with either poly(I:C) or HCV RNA representing the HCV subgenomic replicon induced I-TAC mRNA expression. HCV replication was also found to modulate I-TAC expression, with stimulation of Huh-7 cells harboring either the HCV subgenomic or genomic replicon showing significantly increased synergistic effects compared with those previously seen in Huh-7 cells alone with IFN- and TNF-. In conclusion, these results suggest I-TAC, one of the most potent chemoattractants for activated T cells, is produced by hepatocytes in the HCV-infected liver and plays an important role in T cell recruitment and ultimately the pathogenesis of CHC. |
Keywords: | Cell Line, Tumor Hepatocytes Humans Hepacivirus Hepatitis C, Chronic Carcinoma, Hepatocellular Liver Neoplasms Interferon-alpha Receptors, Chemokine RNA, Double-Stranded RNA, Messenger RNA, Viral Chemokines, CXC Antiviral Agents Gene Expression Up-Regulation Replicon Receptors, CXCR3 Chemokine CXCL11 Interferon-gamma In Vitro Techniques |
Description: | The definitive version may be found at www.wiley.com |
DOI: | 10.1002/hep.20167 |
Published version: | http://www3.interscience.wiley.com/cgi-bin/abstract/108561454 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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