Wasmuth, Hermann E. and Zaldivar, Mirko Moreno and Berres, Marie-Luise and Werth, Alexa and Scholten, David and Hillebrandt, Sonja and Tacke, Frank and Schmitz, Petra and Dahl, Edgar and Wiederholt, Tonio and Hellerbrand, Claus and Berg, Thomas and Weiskirchen, Ralf and Trautwein, Christian and Lammert, Frank (2008) The fractalkine receptor CX3CR1 is involved in due to chronic hepatitis C infection. JOURNAL OF HEPATOLOGY, 48 (2). pp. 208-215. ISSN 0168-8278, 1600-0641
Full text not available from this repository. (Request a copy)Abstract
Background/Aims: The chemokine receptor CX3CR1 and its specific ligand fractalkine (CX3CL1) are known to modulate inflammatory and fibroproliferative diseases. Here we investigate the role of CX3CR1/fractalkine in HCV-induced liver fibrosis. Methods: A genotype analysis of CX3CR1 variants was performed in 211 HCV-infected patients. Hepatic expression of CX3CR1 was studied in HCV-infected livers and isolated liver cell populations by RT-PCR and immunohistochemistry. The effects of fractalkine on mRNA expression of profibrogenic genes were determined in isolated hepatic stellate cells (HSC) and CX3CR1 genotypes were related to intrahepatic TIMP-1 mRNA levels. Results: The intrahepatic mRNA expression of CX3CR1 correlates with the stage of HCV-induced liver fibrosis (P = 0.03). The CX3CR1 coding variant V2491 is associated with advanced liver fibrosis, independent of the T280M variant (P = 0.009). CX3CR1 is present on primary HSC and fractalkine leads to a suppression of tissue inhibitor of metalloproteinase (TIMP)-1 mRNA in HSC (P = 0.03). Furthermore, CX3CR1 genotypes are associated with TIMP-1 mRNA expression in HCV-infected liver (P = 0.03). Conclusions: The results identify the fractalkine receptor CX3CR1 as susceptibility a gene for hepatic fibrosis in HCV infection. The modulation of TIMP-1 expression by fractalkine and CX3CR1 genotypes provides functional support for the observed genotype-phenotype association. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LIVER FIBROSIS; STELLATE CELLS; DISEASE; CHEMOKINE; EXPRESSION; POLYMORPHISM; INJURY; RECRUITMENT; MECHANISMS; CX(3)CR1; liver fibrosis; CX3CR1; fractalkine; genetic predisposition; immunology; hepatic stellate cells; hepatitis C; chemokines |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Nov 2020 07:15 |
| Last Modified: | 10 Nov 2020 07:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/31429 |
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