title: Interleukin-6 sustains hepatic regeneration in cirrhotic rat.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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-kappaB 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 alpha/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-kappaB 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.
authors.affiliation: Surgical Clinic, Department of Medical and Surgical Sciences, University of Brescia, Italy. guido.tiberio@libero.it
authors.forename: Guido Alberto Massimo
authors.initials: GA
authors.lastname: Tiberio
authors.forename: Laura
authors.initials: L
authors.lastname: Tiberio
authors.forename: Anna
authors.initials: A
authors.lastname: Benetti
authors.forename: Edoardo
authors.initials: E
authors.lastname: Cervi
authors.forename: Giampietro
authors.initials: G
authors.lastname: Pandolfo
authors.forename: Michel
authors.initials: M
authors.lastname: Dreano
authors.forename: Gianni
authors.initials: G
authors.lastname: Garotta
authors.forename: Laura
authors.initials: L
authors.lastname: Comini
authors.forename: Marika
authors.initials: M
authors.lastname: Martini
authors.forename: Stefano Maria
authors.initials: SM
authors.lastname: Giulini
authors.forename: Luisa
authors.initials: L
authors.lastname: Schiaffonati
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000032:analysis; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism*; D008115:Liver Regeneration; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D014157:Transcription Factors; C113250:interleukin-6 receptor alpha; D050822:Cytokine Receptor gp130; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D001973:Bromodeoxyuridine