Nuclear migration of NF-κB correlates with TNF-α mRNA accumulation

H. Albrecht, Lawrence B Schook, C. V. Jongeneel

Research output: Contribution to journalArticle

Abstract

Previous work on the transcriptional regulation of the mouse TNF-α promoter had indicated a major role for the NF-κB transcription factor in the induction of the gene by endotoxin. However, similar studies using the human promoter failed to establish a role for this factor. We measured the nuclear migration of NF-κB and the accumulation of TNF-α mRNA in murine T lymphoblasts and bone marrow- derived macrophages (BMDM) under different activation conditions, seeking to establish a correlation. Activation of NF-κB and accumulation of TNF-α mRNA correlated semiquantitatively under the following conditions: (1) inhibition of NF-κB by dithiocarbamates; (2) induction of TNF synthesis by taxol; (3) partial induction of TNF-α mRNA by various inducers in macrophages from lps(d) mice; and (4) inhibition of NF-κB activation by a protease inhibitor. However, inhibition of TNF-α mRNA accumulation by cAMP inducers had no effect on NF-κB induction. We conclude that NF-κB translocation is necessary, but not sufficient for the transcriptional induction of the TNF-α gene by LPS in macrophages or by phorbol ester and ionomycin in T lymphocytes.

Original languageEnglish (US)
Pages (from-to)64-71
Number of pages8
JournalJournal of Inflammation
Volume45
Issue number1
StatePublished - 1995

Keywords

  • cAMP inducers
  • LPS
  • NK-κB
  • TNF-α
  • transcriptional regulation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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