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

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 Brancaccio, Vittorio E. Andreucci, Riccardo d'Agostino, Enrico Drioli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)4836-4844
Number of pages9
JournalBiomaterials
Volume28
Issue number32
DOIs
Publication statusPublished - Nov 2007

Keywords

  • Bioreactor
  • Fetuin-A
  • Galactosylated membrane
  • Hepatocytes
  • IL-6
  • Inflammation

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

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  • Cite this

    Memoli, B., De Bartolo, L., Favia, P., Morelli, S., Lopez, L. C., Procino, A., Barbieri, G., Curcio, E., Giorno, L., Esposito, P., Cozzolino, M., Brancaccio, D., Andreucci, V. E., d'Agostino, R., & Drioli, E. (2007). Fetuin-A gene expression, synthesis and release in primary human hepatocytes cultured in a galactosylated membrane bioreactor. Biomaterials, 28(32), 4836-4844. https://doi.org/10.1016/j.biomaterials.2007.05.043