Cytokine gene expression in liver following minor or major hepatectomy in rat.
Interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), and transforming growth factors alpha and beta (TGF-alpha and TGF-beta) 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 sacrificed 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-alpha, no significant changes were observed between groups. Growth factor expression differed according to the extent of hepatic resection. Moreover, plasma levels of alpha2-macroglobulin (alpha2M) and alpha1 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, alpha2M 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.
Scotté
M
M
Inserm U78, Boisguillaume, France.
Masson
S
S
Lyoumi
S
S
Hiron
M
M
Ténière
P
P
Lebreton
J P
JP
Daveau
M
M
D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D006498:Hepatectomy; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008115:Liver Regeneration; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000209:Acute-Phase Proteins; D016207:Cytokines; D006133:Growth Substances; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha