Nuclear migration of NF-kappa B correlates with TNF-alpha mRNA 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 studies using the human promoter failed to establish a role for this factor. We measured the nuclear migration of NF-kappa B and the accumulation of TNF-alpha mRNA in murine T lymphoblasts and bone marrow-derived macrophages (BMDM) under different activation conditions, seeking to establish a correlation. Activation of NF-kappa B and accumulation of TNF-alpha mRNA correlated semiquantitatively under the following conditions: (1) inhibition of NF-kappa B by dithiocarbamates; (2) induction of TNF synthesis by taxol; (3) partial induction of TNF-alpha mRNA by various inducers in macrophages from lpsd 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-kappa B induction. We conclude that NF-kappa B translocation is necessary, but not sufficient for the transcriptional induction of the TNF-alpha gene by LPS in macrophages or by phorbol ester and ionomycin in T lymphocytes.
Albrecht
H
H
Ludwig Institute for Cancer Research, University of Lausanne, Switzerland.
Schook
L B
LB
Jongeneel
C V
CV
D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D001854:Bone Marrow Cells; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism / Q000648:ultrastructure; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D016166:Free Radical Scavengers; D016328:NF-kappa B; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D014108:Tosylphenylalanyl Chloromethyl Ketone; D000242:Cyclic AMP; D017239:Paclitaxel; D015739:Nocodazole