Fetuin-A gene expression, synthesis and release in primary human hepatocytes cultured in a galactosylated membrane bioreactor

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• 作者：Bruno Memoli ; Loredana De Bartolo ; Pietro Favia ; Sabrina Morelli ; Linda C. Lopez ; Alfredo Procino ; Giuseppe Barbieri ; Efrem Curcio ; Lidietta Giorno ; Pasquale Esposito ; Mario Cozzolino ; Diego Brancacci
• 关键词：Fetuin-A ; IL-6 ; Inflammation ; Hepatocytes ; Bioreactor ; Galactosylated membrane
• 刊名：Biomaterials
• 出版年：2007
• 出版时间：November 2007
• 年：2007
• 卷：28
• 期：32
• 页码：4836-4844
• 全文大小：627 K

文摘

This paper reports on human hepatocytes cultured in a galactosylated membrane bioreactor in order to explore the modulation of the effects of a pro-inflammatory cytokine, Interleukin-6 (IL-6) on the liver cells at molecular level. In particular the role of IL-6 on gene expression and production of a glycoprotein, fetuin-A produced by hepatocytes, was investigated by culturing hepatocytes in the membrane bioreactor, both in the absence and presence of IL-6 (300 pg/ml).

IL-6 modulated the fetuin-A gene expression, synthesis and release by primary human hepatocytes cultured in the bioreactor. A 75 % IL-6-induced reduction of fetuin-A concentration in the medium was associated with a 60 % increase of C-reactive protein in the same samples. Real-time-PCR demonstrated an 8-fold IL-6-induced reduction of fetuin-A gene expression. These results demonstrate that the hepatocyte galactosylated membrane bioreactor is a valuable tool to study IL-6 effects and gave evidence, for the first time, that IL-6 down-regulates the gene expression and synthesis of fetuin-A by primary human hepatocytes. The human hepatocyte bioreactor behaves like the in vivo liver, reproducing the same hepatic acute-phase response that occurs during the inflammatory process.