title: TNF-inducible expression of lymphotoxin-β in hepatic cells: an essential role for NF-κB and Ets1 transcription factors.
abstract: As TNF is one of the earliest signals that can be detected in the leukocyte-derived inflammatory cascade which drives subsequent cytokine production, we are interested in determining whether TNF is one of the initiating factors controlling liver remodeling and regeneration following chronic liver damage. One of the early responses is the expression of lymphotoxin-β by hepatic progenitor oval cells. The aim of this study was to determine whether hepatic expression of LT-β was controlled by TNF and to understand the basis of this regulation. We previously showed that LT-β expression is transcriptionally controlled via the TNF-induced, inflammatory NF-κB pathway in T lymphocytes. Here we show that TNF is able to upregulate LT-β expression in hepatic cells at the transcriptional level by the binding of NF-κB p50/p65 heterodimers and Ets1 to their respective sites in the LT-β promoter.
authors: Biochemistry and Molecular Biology, School of Chemistry and Biochemistry, The University of Western Australia, Crawley 6009, Australia.
authors: Lily S
authors: LS
authors: Subrata
authors: Dominic C
authors: DC
authors: Voon
authors: George C T
authors: GC
authors: Yeoh
authors: Daniela
authors: D
authors: Ulgiati
authors: Elizabeth A
authors: EA
authors: Quail
authors: Lawrence J
authors: LJ
authors: Abraham
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D053308:Lymphotoxin-beta / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D055503:Protein Multimerization / Q000187:drug effects / Q000235:genetics; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D051766:Early Growth Response Protein 1; D053308:Lymphotoxin-beta; D016328:NF-kappa B; D050784:Proto-Oncogene Protein c-ets-1; D016329:Sp1 Transcription Factor; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate