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

被引:20
作者
Alpini, G
Ueno, Y
Tadlock, L
Glaser, SS
LeSage, G
Francis, H
Taffetani, S
Marzioni, M
Alvaro, D
Patel, T
机构
[1] Texas A&M Univ Syst, Hlth Sci Ctr, Coll Med, Temple, TX 76504 USA
[2] Scott & White Mem Hosp & Clin, Dept Internal Med, Temple, TX 76504 USA
[3] Scott & White Mem Hosp & Clin, Dept Med Phys, Temple, TX 76504 USA
[4] Scott & White Mem Hosp & Clin, Div Res & Educ, Temple, TX 76504 USA
[5] Cent Texas Vet Hlth Care Syst, Temple, TX 76504 USA
[6] Tohoku Univ, Sch Med, Div Gastroenterol, Sendai, Miyagi 9808574, Japan
[7] Univ Roma La Sapienza, Div Gastroenterol, I-00185 Rome, Italy
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2003年 / 285卷 / 01期
关键词
apoptosis; bile flow; intrahepatic biliary epithelium; proliferation; secretin;
D O I
10.1152/ajpcell.00497.2002
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:C183 / C194
页数:12
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