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. 2008 Feb;48(2):208-15.
doi: 10.1016/j.jhep.2007.09.008. Epub 2007 Nov 20.

The fractalkine receptor CX3CR1 is involved in liver fibrosis due to chronic hepatitis C infection

Hermann E Wasmuth  1 , Mirko Moreno Zaldivar, Marie-Luise Berres, Alexa Werth, David Scholten, Sonja Hillebrandt, Frank Tacke, Petra Schmitz, Edgar Dahl, Tonio Wiederholt, Claus Hellerbrand, Thomas Berg, Ralf Weiskirchen, Christian Trautwein, Frank Lammert
Affiliations

The fractalkine receptor CX3CR1 is involved in liver fibrosis due to chronic hepatitis C infection

Hermann E Wasmuth et al. J Hepatol. 2008 Feb.

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 V249I 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.

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