title: Lithocholic acid-induced placental tumor necrosis factor-α upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy.
abstract: OBJECTIVE
  To investigate tumor necrosis factor (TNF)-α 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-α measurements. Bile acid-induced TNF-α expression and cell apoptosis were evaluated in cultured syncytiotrophoblasts in vitro.
  
  
  RESULTS
  ICP placental trophoblasts displayed apoptotic histological abnormalities. TNF-α 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-α mRNA were positively correlated with serum bile acid concentration in ICP patients. In vitro, lithocholic acid (LCA) significantly enhanced TNF-α mRNA at both doses, by 2.07-fold at 15 μm and by 3.41-fold at 30 μm, whereas deoxycholic acid mildly increased TNF-α mRNA by 1.41-fold at 100 μm only. LCA treatment produced significantly higher percentage of caspase-3 positive cells than vehicle treatment, rescuable by the addition of a TNF-α inhibitor, indicative of apoptosis induced by LCA-TNF-α pathway.
  
  
  CONCLUSIONS
  This study shows that the increase of TNF-α 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.
authors.affiliation: Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Du
authors.forename: Youhua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Youdong
authors.initials: Y
authors.lastname: Pan
authors.forename: Tao
authors.initials: T
authors.lastname: Duan
keywords: bile acid; intrahepatic cholestasis of pregnancy; lithocholic acid syncytiotrophoblast; tumor necrosis factor-α