Increased susceptibility of cholangiocytes to tumor necrosis factor-α cytotoxicity after bile duct ligation

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

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Tumor necrosis factor (TNF)-α plays a critical role in epithelial cell injury. However, the role of TNF-α in mediating cholangiocyte injury under physiological or pathophysiological conditions is unknown. Thus we assessed the effects of TNF-α 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-α 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-α mediates cholangiocyte injury and altered ductal secretion following bile duct ligation. These observations suggest that cholestasis may enhance susceptibility to cytokine-mediated cholangiocyte injury.

Original languageEnglish (US)
Pages (from-to)C183-C194
JournalAmerican Journal of Physiology - Cell Physiology
Volume285
Issue number1 54-1
DOIs
StatePublished - Jul 1 2003

Keywords

  • Apoptosis
  • Bile flow
  • Intrahepatic biliary epithelium
  • Proliferation
  • Secretin

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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