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Du Q, Zhang Y, Pan Y, et al. Lithocholic acid-induced placental tumor necrosis factor-α upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy. Hepatol Res. 2013;44(5):532-41doi: 10.1111/hepr.12150.
Du, Q., Zhang, Y., Pan, Y., & Duan, T. (2014). Lithocholic acid-induced placental tumor necrosis factor-α upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy. Hepatology research : the official journal of the Japan Society of Hepatology, 44(5), 532-41. https://doi.org/10.1111/hepr.12150
Du, Qiaoling, et al. "Lithocholic acid-induced placental tumor necrosis factor-α upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy." Hepatology research : the official journal of the Japan Society of Hepatology vol. 44,5 (2014): 532-41. doi: https://doi.org/10.1111/hepr.12150
Du Q, Zhang Y, Pan Y, Duan T. Lithocholic acid-induced placental tumor necrosis factor-α 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. PMID: 23627780.
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Hepatol Res. 2014 May;44(5):532-41. doi: 10.1111/hepr.12150. Epub 2013 May 31.

Lithocholic acid-induced placental tumor necrosis factor-α upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy.

Hepatology research : the official journal of the Japan Society of Hepatology

Qiaoling Du, Youhua Zhang, Youdong Pan, Tao Duan

Affiliations

  1. Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine.

PMID: 23627780 DOI: 10.1111/hepr.12150

Abstract

AIM: 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.

CONCLUSION: 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.

© 2013 The Japan Society of Hepatology.

Keywords: bile acid; intrahepatic cholestasis of pregnancy; lithocholic acid syncytiotrophoblast; tumor necrosis factor-α

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