Tumor necrosis factor-alpha is a direct hepatocyte mitogen in the rat.
We previously reported that tumor necrosis factor-alpha (TNF-alpha) increases in vivo hepatocyte mitoses and liver regeneration in rats. In the present studies, we used in vitro hepatocyte cultures to determine whether TNF-alpha itself was mitogenic or whether other cytokines (IL-1 beta and IL-6) that share similar actions with TNF-alpha might be involved. Hepatocytes were cultured with TNF-alpha (4, 40 or 400 U/ml), IL-1 beta (0.1, 1 and 10 ng/ml) or IL-6 (0.2, 2, or 20 ng/ml) for 24 h and 3 d. Incorporation of [3H]thymidine was increased significantly by TNF-alpha (40 and 400 U/ml) at 3 d. Both IL-1 beta and IL-6 at all concentrations significantly decreased [3H]thymidine incorporation at 3 d. These results indicate that TNF-alpha has a direct mitogenic action on hepatocytes. In contrast, IL-1 beta and IL-6 appear to suppress DNA synthesis in hepatocytes.
Beyer
H S
HS
Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota.
Theologides
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D000704:Analysis of Variance; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D004247:DNA