title: The fractalkine receptor CX3CR1 is involved in liver fibrosis due to chronic hepatitis C infection.
abstract: OBJECTIVE
  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.
authors: Medical Department III, University Hospital Aachen, Pauwelsstrasse 30, D-52057 Aachen, Germany. hwasmuth@ukaachen.de
authors: Hermann E
authors: HE
authors: Wasmuth
authors: Mirko Moreno
authors: MM
authors: Zaldivar
authors: Marie-Luise
authors: ML
authors: Berres
authors: Alexa
authors: A
authors: Werth
authors: David
authors: D
authors: Scholten
authors: Sonja
authors: S
authors: Hillebrandt
authors: Frank
authors: F
authors: Tacke
authors: Petra
authors: P
authors: Schmitz
authors: Edgar
authors: E
authors: Dahl
authors: Tonio
authors: T
authors: Wiederholt
authors: Claus
authors: C
authors: Hellerbrand
authors: Thomas
authors: T
authors: Berg
authors: Ralf
authors: R
authors: Weiskirchen
authors: Christian
authors: C
authors: Trautwein
authors: Frank
authors: F
authors: Lammert
mesh_terms: D000073883:CX3C Chemokine Receptor 1; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000235:genetics; D006801:Humans; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000209:etiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000032:analysis; D019707:Receptors, Chemokine / Q000235:genetics*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D019715:Tissue Inhibitor of Metalloproteinase-1