Activation of the nuclear factor kappa B is not sufficient for regulation of tumor necrosis factor-induced interleukin-6 gene expression.
After treatment of L929 cells, a murine fibrosarcoma line, with tumor necrosis factor (TNF), a nuclear kappa B-like transcription factor is rapidly induced as identified by gel shift mobility assays using the kappa B-responsive sequence of the immunoglobulin or interleukin-6 (IL-6) genes as a DNA probe. When induction was carried out under conditions of increased or decreased cytotoxicity, which correlates with altered IL-6 gene expression, nuclear factor kappa B (NF-kappa B) activation was also demonstrated, but the abundance of the protein/DNA complex observed remained unchanged. Also activation of NF-kappa B as a function of time following TNF treatment did not reveal a correlation between the abundance of the protein/DNA complex and the TNF-induced IL-6 mRNA levels. Moreover, in L929 cells resistant to TNF cytotoxicity, the kappa B-like factor still became fully activated by TNF, although the IL-6 gene was only marginally expressed. In conclusion, discrepancies between the abundance of the activated NF-kappa B-like factor and the IL-6 mRNA production upon treatment with TNF indicate that (an) additional transcription factor(s) and/or (a) regulating mechanism(s) is (are) necessary for fine regulation of the level of IL-6 gene expression in response to cytokine stimulation.
Patestos
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Laboratory of Molecular Biology, Gent University, Belgium.
Haegeman
G
G
Vandevoorde
V
V
Fiers
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W
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D005354:Fibrosarcoma / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects*; D015850:Interleukin-6 / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015850:Interleukin-6; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha