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 kappaB-like transcription factor is rapidly induced as identified by gel shift mobility assays using the kappaB-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 kappaB (NF-kappaB) activation was also demonstrated, but the abundance of the protein/DNA complex observed remained unchanged. Also activation of NF-kappaB 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 kappaB-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-kappaB-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.