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 language | English (US) |
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Pages (from-to) | C183-C194 |
Journal | American Journal of Physiology - Cell Physiology |
Volume | 285 |
Issue number | 1 54-1 |
DOIs | |
State | Published - Jul 1 2003 |
Keywords
- Apoptosis
- Bile flow
- Intrahepatic biliary epithelium
- Proliferation
- Secretin
ASJC Scopus subject areas
- Physiology
- Cell Biology