Lithocholic acid‐induced placental tumor necrosis factor‐α upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy. Issue 5 (31st May 2013)

• Record Type: Journal Article
• Authors: Du, Qiaoling; Zhang, Youhua; Pan, Youdong; Duan, Tao
• Is Part Of: Hepatology research. Volume 44:Issue 5(2014:May)
• Page Start: 532
• Page End: 541
• Publication Date: 2013-05-31
• Subjects: Liver -- Diseases -- Periodicals; Liver Diseases -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1111/hepr.12150
• Languages: English
• ISSNs: 1386-6346

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="hepr12150-sec-0001" sec-type="section"> <title>Aim</title> <p>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).</p> </sec> <sec id="hepr12150-sec-0002" sec-type="section"> <title>Methods</title> <p>Human placenta, including normal pregnancies (<italic>n</italic> = 10) and patients with ICP (<italic>n</italic> = 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 <italic>in vitro</italic>.</p> </sec> <sec id="hepr12150-sec-0003" sec-type="section"> <title>Results</title> <p>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. <italic>In vitro</italic>, lithocholic acid (LCA) significantly enhanced TNF‐α mRNA at both doses, by 2.07‐fold at 15 μ<sc>m</sc> and by 3.41‐fold at 30 μ<sc>m</sc>, whereas deoxycholic acid mildly increased TNF‐α mRNA by 1.41‐fold at 100 μ<sc>m</sc> 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.</p> </sec> <sec id="hepr12150-sec-0004" sec-type="section"> <title>Conclusion</title> <p>This study shows that the increase of TNF‐α expression in placental trophoblasts is strongly associated with ICP pathology and is inducible by LCA <italic>in vitro</italic>, suggesting its potential value in the clinical prevention, diagnosis and treatment of ICP.</p> </sec> </abstract>