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World J Gastroenterol. Dec 28, 2005; 11(48): 7602-7606
Published online Dec 28, 2005. doi: 10.3748/wjg.v11.i48.7602
Cyclosporine A, FK-506, 40-0-[2-hydroxyethyl]rapamycin and mycophenolate mofetil inhibit proliferation of human intrahepatic biliary epithelial cells in vitro
Christoph E Broelsch, Guido Gerken, Ulrich Treichel, Uta Dahmen, Andrea Frilling, Thomas Schreiter, Chao Liu
Chao Liu, Thomas Schreiter, Guido Gerken, Ulrich Treichel, Department of Gastroenterology and Hepatology, University Hospital Essen, Germany
Andrea Frilling, Uta Dahmen, Christoph E Broelsch, Department of General Surgery and Transplantation, University Hospital Essen, Germany
Chao Liu, Department of General Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 West Yan Jiang Road, 510120 Guangzhou, Guangdong Province, China. mdliuchao@hotmail.com,
Author contributions: All authors contributed equally to the work.
Correspondence to: Ulrich Treichel, MD, Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany. ulrich.treichel@uni-essen.de
Telephone: +49-201-723-3612 Fax: +49-201-723-5970
Received: December 30, 2004
Revised: February 13, 2005
Accepted: February 18, 2005
Published online: December 28, 2005
Abstract

AIM: To investigate the effect of cyclosporine A (CsA), FK-506, and mycophenolate mofetil (MMF) and 40-0-[2-hydroxyethyl]rapamycin (RAD) on proliferation of human intrahepatic biliary epithelial cells (BECs) in vitro.

METHODS: BECs were isolated from six human liver tissuespecimens with the immunomagnetic separation method and treated with different concentrations of CsA, FK-506, RAD, and MMF in vitro. Proliferation of the cells was measured by MTT assay at 24 and 48 h after treatment, respectively. One-way analysis of variance was used to analyze the results. Expression of CK 19 in BECs was monitored by flow cytometry and Western blot.

RESULTS: Six lines of BECs were established. They survived for 4-18 wk in vitro. Flow cytometry analysis showed that these cells always expressed CK19. CsA, FK-506, RAD, and MMF inhibited proliferation of BECs in a dose-dependent manner. The lowest concentration of CsA, FK-506, RAD, and MMF to inhibit proliferation of BECs (P<0.05) was 500, 100, 0.25, and 100 µg/L, respectively. However, the expression of CK19 by BECs was not changed.

CONCLUSION: CsA, FK-506, RAD, and MMF have an antiproliferative effect on human intrahepatic BECs in vitro, while RAD has the strongest growth-inhibitory effect. Their possible effects on liver regeneration and bile duct injury in transplant patients should be further investigated.

Keywords: Cyclosporine A; FK-506, Rapamycin; Mycophenolate mofetil; Biliary epithelial cells
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