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Am J Physiol Cell Physiol (March 12, 2003). doi:10.1152/ajpcell.00497.2002
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Submitted on October 25, 2002
Accepted on March 10, 2003

Increased Suspceptibility of Cholangiocytes to Tumor Necrosis Factor-{alpha} Cytotoxicity after Bile Duct Ligation

Gianfranco Alpini1, Yoshiyuki Ueno2, Laura Tadlock3, Shannon S Glaser3, Gene LeSage4, Heather Francis3, Silvia Taffetani3, Marco Marzioni5, Domenico Alvaro6, and Tushar Patel4*

1 Internal Medicine, Scott & White Hospital, Temple, TX, USA; Medical Physiology, The Texas A&M University HSC, Temple, TX, USA; Research, Central Texas Veterans Health Care System, Temple, TX, USA
2 Gastroenterology, Tohoku University School of Medicine, Sendai, Japan
3 Research and Education, Scott & White Hospital, Temple, TX, USA
4 Internal Medicine, Scott & White Hospital, Temple, TX, USA
5 Medical Physiology, The Texas A&M University HSC, Temple, TX, USA
6 Gastroenterology, University of Rome,, Temple, Italy

* To whom correspondence should be addressed. E-mail: tpatel{at}swmail.sw.org.

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 are 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, pre-sensitization 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.




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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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