Author/Authors :
Bruno Memoli، نويسنده , , Loredana De Bartolo، نويسنده , , Pietro Favia، نويسنده , , Sabrina Morelli، نويسنده , , Linda C. Lopez، نويسنده , , Alfredo Procino، نويسنده , , Giuseppe Barbieri، نويسنده , , Efrem Curcio، نويسنده , , Lidietta Giorno، نويسنده , , Pasquale Esposito، نويسنده , , Mario Cozzolino، نويسنده , , Diego Brancaccio، نويسنده , , Vittorio E. Andreucci، نويسنده , , Riccardo d’Agostino، نويسنده , , Enrico Drioli ، نويسنده ,
Abstract :
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.
Keywords :
hepatocytes , bioreactor , Galactosylated membrane , Fetuin-A , IL-6 , inflammation