Lithocholic acid-induced placental tumor necrosis factor-alpha upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy.
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Du Q, Zhang Y, Pan Y, Duan T
Lithocholic acid-induced placental tumor necrosis factor-alpha upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy.
Hepatol Res. 2014 May;44(5):532-41. doi: 10.1111/hepr.12150. Epub 2013 May 31.
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- 23627780 [ View in PubMed]
- Abstract
AIM: To investigate tumor necrosis factor (TNF)-alpha expression and its relationship with serum bile acids in placental trophoblasts from patients with intrahepatic cholestasis of pregnancy (ICP). METHODS: Human placenta, including normal pregnancies (n = 10) and patients with ICP (n = 10), were collected at term and subject to TNF-alpha measurements. Bile acid-induced TNF-alpha expression and cell apoptosis were evaluated in cultured syncytiotrophoblasts in vitro. RESULTS: ICP placental trophoblasts displayed apoptotic histological abnormalities. TNF-alpha levels in ICP tissue were significantly greater than those of controls as measured by quantitative polymerase chain reaction and western blot. Levels of placental TNF-alpha mRNA were positively correlated with serum bile acid concentration in ICP patients. In vitro, lithocholic acid (LCA) significantly enhanced TNF-alpha mRNA at both doses, by 2.07-fold at 15 mum and by 3.41-fold at 30 mum, whereas deoxycholic acid mildly increased TNF-alpha mRNA by 1.41-fold at 100 mum only. LCA treatment produced significantly higher percentage of caspase-3 positive cells than vehicle treatment, rescuable by the addition of a TNF-alpha inhibitor, indicative of apoptosis induced by LCA-TNF-alpha pathway. CONCLUSION: This study shows that the increase of TNF-alpha expression in placental trophoblasts is strongly associated with ICP pathology and is inducible by LCA in vitro, suggesting its potential value in the clinical prevention, diagnosis and treatment of ICP.