title: Up-regulated expression of fractalkine and its receptor CX3CR1 during liver injury in humans.
abstract: OBJECTIVE
  Little is known about the role of fractalkine (CX3CL1) in the liver. The aim of this study was to investigate the expression patterns of fractalkine and its receptor CX3CR1 in normal human liver and in conditions of injury.
  
  
  METHODS
  Distribution and expression of fractalkine and its receptor were investigated using immunohistochemistry, in situ hybridization, flow cytometry and reverse transcriptase-polymerase chain reaction. In vitro experiments were conducted in HepG2 cells.
  
  
  RESULTS
  Both fractalkine and CX3CR1 were up-regulated during chronic injury, in areas of portal and lobular inflammation. In severe acute hepatitis, fractalkine and CX3CR1 were expressed at high levels not only in areas of inflammation but also in regenerating epithelial cells within bile duct-like structures, which showed co-expression of fractalkine and cytokeratin-7 or CX3CR1. The human hepatocarcinoma cell line HepG2 expressed fractalkine at the gene and protein level, and HepG2-conditioned medium was chemotactic for cells overexpressing CX3CR1. Transcripts for CX3CR1 were detected in HepG2, and exposure of these cells to recombinant fractalkine induced cell migration.
  
  
  CONCLUSIONS
  This study shows that the fractalkine system is up-regulated during liver damage, and suggests that fractalkine may play a role in the recruitment and adhesion of inflammatory cells and in the biology of liver epithelial cells.
authors.affiliation: Dipartimento di Medicina Interna, University of Florence, Viale Morgagni 85, I-50134 Florence, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Efsen
authors.forename: Cecilia
authors.initials: C
authors.lastname: Grappone
authors.forename: Raffaella M S
authors.initials: RM
authors.lastname: DeFranco
authors.forename: Stefano
authors.initials: S
authors.lastname: Milani
authors.forename: Roberto G
authors.initials: RG
authors.lastname: Romanelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Bonacchi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Caligiuri
authors.forename: Paola
authors.initials: P
authors.lastname: Failli
authors.forename: Francesco
authors.initials: F
authors.lastname: Annunziato
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pagliai
authors.forename: Massimo
authors.initials: M
authors.lastname: Pinzani
authors.forename: Giacomo
authors.initials: G
authors.lastname: Laffi
authors.forename: Paolo
authors.initials: P
authors.lastname: Gentilini
authors.forename: Fabio
authors.initials: F
authors.lastname: Marra
mesh_terms: D000208:Acute Disease; D000073883:CX3C Chemokine Receptor 1; D006528:Carcinoma, Hepatocellular; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000235:genetics*; D004847:Epithelial Cells / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006526:Hepatitis C / Q000503:physiopathology*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000502:physiology; D008113:Liver Neoplasms; D008115:Liver Regeneration / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D019707:Receptors, Chemokine