Increased susceptibility of cholangiocytes to tumor necrosis factor-alpha cytotoxicity after bile duct ligation. Academic Article uri icon


  • 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.

published proceedings

  • Am J Physiol Cell Physiol

author list (cited authors)

  • Alpini, G., Ueno, Y., Tadlock, L., Glaser, S. S., LeSage, G., Francis, H., ... Patel, T.

citation count

  • 45

complete list of authors

  • Alpini, Gianfranco||Ueno, Yoshiyuki||Tadlock, Laura||Glaser, Shannon S||LeSage, Gene||Francis, Heather||Taffetani, Silvia||Marzioni, Marco||Alvaro, Domenico||Patel, Tushar

publication date

  • July 2003