title: Tumor necrosis factor-alpha induces c-jun during the regenerative response to liver injury.
abstract: After liver injury, remaining hepatocytes proliferate to regenerate the liver. Although the precise mechanisms that initiate and localize regeneration are unknown, local induction of c-jun is a critical, early step in the response. Treatment of rats with antibodies to tumor necrosis factor-alpha (TNF-alpha), a mediator of liver injury, inhibits regenerative induction of jun nuclear kinase activity and nuclear c-jun expression and alters the DNA binding activity of the c-jun transcription factor, AP-1, in liver. Pretreatment with anti-TNF antibodies does not affect pulmonary or renal c-jun expression or AP-1 binding activity post-partial hepatectomy. In primary hepatocyte cultures, TNF-alpha directly promotes the proliferative actions of mitogens, supporting in vivo evidence that it sensitizes hepatocytes to mitogens. Thus local release of TNF may act in a paracrine fashion to initiate regeneration in the injured liver by promoting induction of critical growth-related genes, such as c-jun.
authors.affiliation: Johns Hopkins University, Baltimore, Maryland 21205.
authors.forename: A M
authors.initials: AM
authors.lastname: Diehl
authors.forename: M
authors.initials: M
authors.lastname: Yin
authors.forename: J
authors.initials: J
authors.lastname: Fleckenstein
authors.forename: S Q
authors.initials: SQ
authors.lastname: Yang
authors.forename: H Z
authors.initials: HZ
authors.lastname: Lin
authors.forename: D A
authors.initials: DA
authors.lastname: Brenner
authors.forename: J
authors.initials: J
authors.lastname: Westwick
authors.forename: G
authors.initials: G
authors.lastname: Bagby
authors.forename: S
authors.initials: S
authors.lastname: Nelson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001483:Base Sequence; D004247:DNA / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects*; D016758:Genes, jun; D006498:Hepatectomy / Q000379:methods; D008099:Liver / Q000293:injuries*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D015345:Oligonucleotide Probes; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D004247:DNA