CX3CL1 (fractalkine): A signpost for biliary inflammation in primary biliary cirrhosis

Shinji Shimoda, Kenichi Harada, Hiroaki Niiro, Akinobu Taketomi, Yoshihiko Maehara, Koichi Tsuneyama, Kentaro Kikuchi, Yasuni Nakanuma, Ian R. Mackay, M. Eric Gershwin, Koichi Akashi

研究成果: ジャーナルへの寄稿記事

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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 α(TNF-α). 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. Conclusion: 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-α; 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.

元の言語英語
ページ(範囲)567-575
ページ数9
ジャーナルHepatology
51
発行部数2
DOI
出版物ステータス出版済み - 2 1 2010

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All Science Journal Classification (ASJC) codes

  • Hepatology

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