NUCLEAR MIGRATION OF NF-KAPPA-B CORRELATES WITH TNF-ALPHA MESSENGER-RNA ACCUMULATION

Previous work on the transcriptional regulation of the mouse TNF-alpha promoter had indicated a major role for the NF-kappa B transcription factor in the induction of the gene by endotoxin. However, similar stu dies using the human promoter failed to establish a role for this fact or. We measured the nuclear migration of NF-kappa B and the accumulati on of TNF-alpha mRNA in murine T lymphoblasts and bone marrow-derived macrophages (BMDM) under different activation conditions, seeking to e stablish a correlation Activation of NF-kappa B and accumulation of TN F-alpha mRNA correlated semiquantitatively under the following conditi ons: (1) inhibition of NF-kappa B by dithiocarbamates; (2) induction o f TNF synthesis by taxol; (3) partial induction of TNF-alpha mRNA by v arious inducers in macrophages from lps(d) mice; and (4) inhibition of NF-kappa B activation by a protease inhibitor. However, inhibition of TNF-alpha mRNA accumulation by cAMP inducers had no effect on NF-kapp a B induction. We conclude that NF-kappa B translocation is necessary, bur not sufficient for the transcriptional induction of the TNF alpha gene by LPS in macrophages or by phorbol ester and ionomycin in T lym phocytes. (C) 1995 Wiley-Liss, Inc.