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Am J Physiol Cell Physiol 285: C183-C194, 2003. First published March 12, 2003; doi:10.1152/ajpcell.00497.2002
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GROWTH, DIFFERENTIATION, AND APOPTOSIS

Increased susceptibility of cholangiocytes to tumor necrosis factor-{alpha} cytotoxicity after bile duct ligation

Gianfranco Alpini,1,2,3 Yoshiyuki Ueno,4 Laura Tadlock,5 Shannon S. Glaser,5 Gene LeSage,1 Heather Francis,5 Silvia Taffetani,5 Marco Marzioni,2 Domenico Alvaro,6 and Tushar Patel1

Departments of 1Internal Medicine and 2Medical Physiology, 5Division of Research and Education, Scott & White Clinic and The Texas A&M University System Health Science Center, College of Medicine, and 3Central Texas Veterans Health Care System, Temple, Texas 76504; 4Division of Gastroenterology, Tohoku University School of Med, Aobaku, Sendai 980-8574, Japan; and 6Division of Gastroenterology, University of Rome, "La Sapienza," Rome 00185, Italy

Submitted 25 October 2002 ; accepted in final form 10 March 2003

Tumor necrosis factor (TNF)-{alpha} plays a critical role in epithelial cell injury. However, the role of TNF-{alpha} in mediating cholangiocyte injury under physiological or pathophysiological conditions is unknown. Thus we assessed the effects of TNF-{alpha} alone or following sensitization by actinomycin D on cell apoptosis, proliferation, and basal and secretin-stimulated ductal secretion in cholangiocytes from normal or bile duct-ligated (BDL) rats. Cholangiocytes from normal or BDL rats were highly resistant to TNF-{alpha} alone. However, presensitization by actinomycin D increased apoptosis in cholangiocytes following BDL and was associated with an inhibition of proliferation and secretin-stimulated ductal secretion. Thus TNF-{alpha} mediates cholangiocyte injury and altered ductal secretion following bile duct ligation. These observations suggest that cholestasis may enhance susceptibility to cytokine-mediated cholangiocyte injury.

bile flow; intrahepatic biliary epithelium; proliferation; secretin


Address for reprint requests and other correspondence: T. Patel, Division of Gastroenterology, Scott & White Clinic, Texas A&M Univ. System Health Science Center College of Medicine, 2401 South 31st St., Temple, TX 76502 (E-mail: tpatel{at}medicine.tamu.edu).




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Y. Ueno, H. Francis, S. Glaser, S. DeMorrow, J. Venter, A. Benedetti, G. Fava, M. Marzioni, and G. Alpini
Taurocholic Acid Feeding Prevents Tumor Necrosis Factor-{alpha}-Induced Damage of Cholangiocytes by a PI3K-Mediated Pathway
Experimental Biology and Medicine, July 1, 2007; 232(7): 942 - 949.
[Abstract] [Full Text] [PDF]


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