TY - JOUR
T1 - Interleukin-6 sustains hepatic regeneration in cirrhotic rat
AU - Tiberio, Guido Alberto Massimo
AU - Tiberio, Laura
AU - Benetti, Anna
AU - Cervi, Edoardo
AU - Pandolfo, Giampietro
AU - Dreano, Michel
AU - Garotta, Gianni
AU - Comini, Laura
AU - Martini, Marika
AU - Giulini, Stefano Maria
AU - Schiaffonati, Luisa
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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.
KW - AKT
KW - eNOS
KW - Hepatocyte proliferation
KW - IL-6 receptors
KW - Transcription factors
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M3 - Article
C2 - 17591083
AN - SCOPUS:34250183381
VL - 54
SP - 878
EP - 883
JO - Acta hepato-splenologica
JF - Acta hepato-splenologica
SN - 0172-6390
IS - 75
ER -