Normal liver regeneration and liver cell apoptosis after partial hepatectomy in tumor necrosis factor-alpha-deficient mice.
OBJECTIVE
Tumor necrosis factor-alpha (TNF-alpha) is known as a proinflammatory cytokine that has been implicated as a contributing factor in a number of disease processes. TNF-alpha 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-alpha influences liver cell apoptosis and regeneration following PH in TNF-alpha-deficient (TNF-alpha(-/-)) mice.


METHODS
PH was performed in wild mice and TNF-alpha(-/-) 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-alpha(+/+) and TNF-alpha(-/-) mice. Few terminal deoxynucleotidyl transferase nick end-labeling-positive hepatocytes were seen in either type of mice. Nuclear factor-kappa B DNA binding activity in the remaining liver of TNF-alpha(-/-) mice after PH was similar to that of control mice. Ribonuclease protection assay showed that transforming growth factor beta1 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-alpha(-/-) mice.


CONCLUSIONS
These findings suggest that TNF-alpha has little influence on liver regeneration and liver cell apoptosis after PH in mice.
Hayashi
Hideki
H
First Department of Internal Medicine, Gifu University School of Medicine, Gifu 501-1194, Japan.
Nagaki
Masahito
M
Imose
Motoaki
M
Osawa
Yosuke
Y
Kimura
Kiminori
K
Takai
Shinji
S
Imao
Motohiro
M
Naiki
Takafumi
T
Kato
Tomohiro
T
Moriwaki
Hisataka
H
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001663:Bilirubin / Q000097:blood; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008940:Mitotic Index; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000235:genetics; D015854:Up-Regulation
D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D000410:Alanine Transaminase; D001663:Bilirubin