Tumor necrosis factor alpha promotes nuclear localization of cytokine-inducible CCAAT/enhancer binding protein isoforms in hepatocytes.

Published

Journal Article

Hepatocytes were cultured in the presence of recombinant tumor necrosis factor (TNF) alpha or mutated TNF alpha peptides that specifically activate either p55 or p75 TNF receptors to determine if TNF alpha can activate cytokine-inducible CCAAT/enhancer binding protein (C/EBP) isoforms by post-transcriptional mechanisms that are initiated by TNF receptors. Within 5-10 min after treatment with any of these agents, nuclear concentrations of C/EBP beta and C/EBP delta double and remain 2-4-fold greater than control cultures for 30 min (p < 0.01). Consistent with these results, gel mobility shift assays demonstrate 3-fold increased nuclear C/EBP beta- and C/EBP delta-DNA binding activity in TNF alpha-treated cells, and immunocytochemistry confirms rapid redistribution of these C/EBP isoforms into the nucleus. In contrast, mRNA and whole cell protein concentrations of C/EBP beta and delta are not altered by TNF alpha exposure, and nuclear concentrations of another C/EBP isoform, C/EBP alpha, are decreased by 80%. This novel evidence that TNF alpha initiates post-transcriptional activation of cytokine-inducible C/EBP isoforms identifies a mechanism that enables hepatocytes to respond immediately to inflammatory stress.

Full Text

Duke Authors

Cited Authors

  • Yin, M; Yang, SQ; Lin, HZ; Lane, MD; Chatterjee, S; Diehl, AM

Published Date

  • July 26, 1996

Published In

Volume / Issue

  • 271 / 30

Start / End Page

  • 17974 - 17978

PubMed ID

  • 8663327

Pubmed Central ID

  • 8663327

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.271.30.17974

Language

  • eng

Conference Location

  • United States