Interleukin-6 sustains hepatic regeneration in cirrhotic rat

Guido Alberto Massimo Tiberio, Laura Tiberio, Anna Benetti, Edoardo Cervi, Giampietro Pandolfo, Michel Dreano, Gianni Garotta, Laura Comini, Marika Martini, Stefano Maria Giulini, Luisa Schiaffonati

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Aims: In the liver IL-6 displays growth-inducing and pro-survival activities. We studied the pro-proliferative and protective mechanisms of IL-6 treatment in a model of liver cirrhosis in wild type rat, investigating the theoretical basis for a potential pharmacologic role of IL-6 in cirrhosis. Methodology: We analyzed IL-6 receptors levels in cirrhotic liver. We also studied the activation of signaling pathways downstream IL-6 receptors by analyzing the DNA-binding activity of transcription factors STAT3, AP-1, HNF-1 and NF-κB and the phosphorylation status of AKT and eNOS. We also analyzed hepato-cell proliferation, by determining BrdU incorporation into DNA, and liver mass expansion. Results: We show that liver cells from cirrhotic animals have increased expression of the IL-6 receptor α/gp80. In addition, we show that in cirrhosis the main molecular pathways downstream the receptors are intact and that IL-6 activates STAT3, AP-1 and NF-κB transcription factors, induces AKT and eNOS phosphorylation and increases hepato-cell proliferation and liver mass expansion in a dose-dependent manner. Conclusions: Our data demonstrate that the theoretical basis exists for the therapeutic employment of IL-6 in liver cirrhosis.

Original languageEnglish
Pages (from-to)878-883
Number of pages6
JournalHepato-Gastroenterology
Volume54
Issue number75
Publication statusPublished - Apr 2007

Keywords

  • AKT
  • eNOS
  • Hepatocyte proliferation
  • IL-6 receptors
  • Transcription factors

ASJC Scopus subject areas

  • Gastroenterology

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