Normal liver regeneration and liver cell apoptosis after partial hepatectomy in tumor necrosis factor-α-deficient mice


Masahito Nagaki, MD, PhD,
First Department of Internal Medicine, Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Tel: +81-58-230-6308
Fax: +81-58-230-6310


Abstract: Aims/Background: Tumor necrosis factor-α (TNF-α) is known as a proinflammatory cytokine that has been implicated as a contributing factor in a number of disease processes. TNF-α also influences liver repair following hepatotoxic damage, and regeneration following partial hepatectomy (PH). The aim of this study was to assess the mechanism by which TNF-α influences liver cell apoptosis and regeneration following PH in TNF-α-deficient (TNF-α−/−) mice.

Methods: PH was performed in wild mice and TNF-α−/− mice.

Results: In both groups, serum alanine aminotransferase and serum total bilirubin levels comparably peaked at 6 and 48 h after PH, respectively. No differences were observed in hepatocyte proliferation, as determined by mitotic and the proliferating cell nuclear antigen labeling indices, between TNF-α+/+ and TNF-α−/− mice. Few terminal deoxynucleotidyl transferase nick end-labeling-positive hepatocytes were seen in either type of mice. Nuclear factor-κB DNA binding activity in the remaining liver of TNF-α−/− mice after PH was similar to that of control mice. Ribonuclease protection assay showed that transforming growth factor β1 mRNA was up-regulated comparably in the livers of the two groups, and that other cytokines were hardly seen in either. Interleukin-6/ signal transducer and activator of transcription-3-dependent pathway was not affected in TNF-α−/− mice.

Conclusions: These findings suggest that TNF-α has little influence on liver regeneration and liver cell apoptosis after PH in mice.