Up-regulated expression of fractalkine and its receptor CX3CR1 during liver injury in humans.
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.
Efsen
Eva
E
Dipartimento di Medicina Interna, University of Florence, Viale Morgagni 85, I-50134 Florence, Italy.
Grappone
Cecilia
C
DeFranco
Raffaella M S
RM
Milani
Stefano
S
Romanelli
Roberto G
RG
Bonacchi
Andrea
A
Caligiuri
Alessandra
A
Failli
Paola
P
Annunziato
Francesco
F
Pagliai
Gabriella
G
Pinzani
Massimo
M
Laffi
Giacomo
G
Gentilini
Paolo
P
Marra
Fabio
F
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
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