Mechanisms of hepatic toxicity. I. TNF-induced liver injury.
Tumor necrosis factor-alpha (TNF-alpha) functions as a two-edged sword in the liver. TNF-alpha is required for normal hepatocyte proliferation during liver regeneration. It functions both as a comitogen and to induce the transcription factor nuclear factor-kappaB, which has antiapoptotic effects. On the other hand, TNF-alpha is the mediator of hepatotoxicity in many animal models, including those involving the toxins concanavalin A and lipopolysaccharide. TNF-alpha has also been implicated as an important pathogenic mediator in patients with alcoholic liver disease and viral hepatitis.
Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7080, USA.
C A
CA
Bradham
J
J
Plümpe
M P
MP
Manns
D A
DA
Brenner
C
C
Trautwein
D000818:Animals; D017209:Apoptosis; D006525:Hepatitis, Viral, Human / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D008099:Liver / Q000473:pathology* / Q000502:physiology; D008108:Liver Diseases, Alcoholic / Q000276:immunology / Q000503:physiopathology; D008115:Liver Regeneration; D008954:Models, Biological; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha