CYTOKINE GENE EXPRESSION IN LIVER FOLLOWING MINOR OR MAJOR HEPATECTOMY IN RAT

Autor: *, Michel Scotté, †, ‡, *, Sylvie Masson, †, *, Saïd Lyoumi, †, *, Martine Hiron, †, Ténière, Paul
Zdroj: Cytokine; November, 1997, Vol. 9 Issue: 11 p859-867, 9p
Abstrakt: Interleukin 6 (IL-6), tumour necrosis factor α (TNF-α), interleukin 1 (IL-1), and transforming growth factors α and β (TGF-α and TGF-β) are important mediators which play a pleiotropic role in both inflammatory and hepatic regeneration processes. It has also been proposed that a major hepatectomy impairs the liver-related host defence mechanisms. The aim of this study was to evaluate the influence of minor (30%) vs major (80%) hepatectomy on cytokines, growth factors and acute-phase proteins both at the protein and mRNA levels in rat. For that purpose, rats were submitted to either 30% or 80% hepatectomy and sacrified at intervals up to day 14 post-hepatectomy to collect liver and blood samples. Serum levels of IL-6 and acute-phase proteins (APPs) were determined after RNA extraction, cytokine and acute-phase proteins gene expression were evaluated using a quantitative RT-PCR method. The results demonstrate that liver mRNA levels for IL-6 were early unregulated after a 80% resection only, whereas liver mRNA levels for IL-1 slowly increased following 30 or 80% hepatectomy. For TNF-α, no significant changes were observed between groups. Growth factor expression differed according to the extent of hepatic resection. Moreover, plasma levels of α2-macroglobulin (α2M) and α1 acid glycoprotein (AGP), two major APPs which respond differently to combination of cytokines, were significantly lowered after a major resection whereas levels of serum IL-6 showed no significant changes between groups. Paradoxically, in the 80% hepatectomized group, α2M mRNA expression was strongly increased at 4 h and 6 h post-hepatectomy as compared with the 30% hepatectomized group. Taken together, these results suggest that, although an increased level of hepatic IL-6 expression was observed following a major resection, the liver's capacity to synthesize normal levels of APPs was impaired. Moreover, these specific changes of cytokine gene expression seen in the liver following major hepatectomy might reflect a preferential activation of the IL-6-dependent APPs.Copyright 1997 Academic Press Limited
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