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 c ritical component in signal transduction pathways. We used an electrop horetic gel mobility shift assay to examine the activation of NF-kappa B in human U-937 cells treated with tumor necrosis factor (TNF), lymp hotoxin (LT), interferons (IFN)-alpha, IFN-beta, and IFN-gamma, interl eukins (IL)-1 beta, IL-4, and IL-6, leukemia inhibitory factor (LIF), basic fibroblast growth factor (FGF), granulocyte-macrophage colony-st imulating factor (GM-CSF), and transforming growth factor-beta (TGF-be ta). Only TNF, LT, and IL-1 activated NF-kappa B. Since interferons ha ve been shown to induce TNF receptors and potentiate TNF-mediated cell ular responses, we also measured the effect of interferons on TNF-indu ced activation of NF-kappa B. Under our conditions, all three IFNs pot entiated the cytotoxic effects of TNF but had no effect on the TNF-dep endent NF-kappa B activation. These results suggest overall that the a ctivation of NF-kappa B is not a generalized mediator of signal transd uction of most cytokines and also that NF-kappa B activation is not su fficient for antiproliferative effects mediated through certain cytoki nes.