Abstract: 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.
Increased Suspceptibility of Cholangiocytes to Tumor Necrosis Factor-{alpha} Cytotoxicity after Bile Duct Ligation / Alpini, G; Ueno, Y; Tadlock, L; Glaser, S; Lesage, G; Francis, H; Taffetani, S; Marzioni, M; Alvaro, Domenico; Patel, T.. - In: AMERICAN JOURNAL OF PHYSIOLOGY. - ISSN 0002-9513. - 285 (1):(2003), pp. C183-C194. [10.1152/ajpcell.00497.2002]
Increased Suspceptibility of Cholangiocytes to Tumor Necrosis Factor-{alpha} Cytotoxicity after Bile Duct Ligation.
ALVARO, Domenico;
2003
Abstract
Abstract: 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
