Effect of tumor necrosis factors, interferons, interleukins, and growth factors on the activation of NF-kappa B: evidence for lack of correlation with cell proliferation.
The nuclear transcription factor NF-kappa B has been identified as a critical component in signal transduction pathways. We used an electrophoretic gel mobility shift assay to examine the activation of NF-kappa B in human U-937 cells treated with tumor necrosis factor (TNF), lymphotoxin (LT), interferons (IFN)-alpha, IFN-beta, and IFN-gamma, interleukins (IL)-1 beta, IL-4, and IL-6, leukemia inhibitory factor (LIF), basic fibroblast growth factor (FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and transforming growth factor-beta (TGF-beta). Only TNF, LT, and IL-1 activated NF-kappa B. Since interferons have been shown to induce TNF receptors and potentiate TNF-mediated cellular responses, we also measured the effect of interferons on TNF-induced activation of NF-kappa B. Under our conditions, all three IFNs potentiated the cytotoxic effects of TNF but had no effect on the TNF-dependent NF-kappa B activation. These results suggest overall that the activation of NF-kappa B is not a generalized mediator of signal transduction of most cytokines and also that NF-kappa B activation is not sufficient for antiproliferative effects mediated through certain cytokines.
Chaturvedi
M M
MM
Department of Clinical Immunology and Biological Therapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Higuchi
M
M
Aggarwal
B B
BB
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D006133:Growth Substances; D007378:Interleukins; D008233:Lymphotoxin-alpha; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D007372:Interferons