title: CX3CL1 (fractalkine): a signpost for biliary inflammation in primary biliary cirrhosis.
abstract: Improvements in the treatment of primary biliary cirrhosis (PBC) may depend upon dissection of mechanisms that determine recruitment of mononuclear cells to intralobular bile ducts, including the role of the chemokine-adhesion molecule CX3CL1 (fractalkine). We submit that there are unique interactions between intrahepatic biliary epithelial cells (BECs), endothelial cells (ECs), liver sinusoidal endothelial cells (LSECs), and liver-infiltrating mononuclear cells (LMCs), and that such interactions will in part dictate the biliary-specific inflammatory response. To address this, we studied fresh explanted livers from pretransplantation patients with PBC and with inflammatory liver disease due to viral infection (disease controls) and biopsy material from patients with a discrete liver tumor (normal controls). Using this clinical material, we isolated and stimulated BECs, ECs, LSECs, and LMCs with a panel of Toll-like receptor ligands. We also studied the interactions of these cell populations with LMCs with respect to adhesion capability and production of tumor necrosis factor alpha (TNF-alpha). Finally, we used fresh biopsy samples to evaluate mononuclear cells around intrahepatic biliary ductules using monoclonal antibodies specific to CD68 or CD154, markers for monocytes/macrophages, and activated T cells, respectively.
  
  
  CONCLUSIONS
  There are common properties of ECs, LSECs, and BECs, whether derived from PBC or viral hepatitis, but there are also significant differences, particularly in the potential in PBC for LMCs to adhere to ECs and BECs and to produce TNF-alpha; such properties were associated with augmented CX3CL1 production by BEC from PBC liver. The processes defined herein suggest potential novel biotherapies for biliary specific inflammation.
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. sshimoda@intmed1.med.kyushu-u.ac.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimoda
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Niiro
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.forename: Ian R
authors.initials: IR
authors.lastname: Mackay
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
mesh_terms: D054428:Chemokine CX3CL1 / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D008099:Liver / Q000166:cytology; D008105:Liver Cirrhosis, Biliary / Q000209:etiology*; D009000:Monocytes / Q000502:physiology
chemical_list: C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1