ACTIVATION OF THE TRANSCRIPTION FACTOR NF-KAPPA-B IN LIPOPOLYSACCHARIDE-STIMULATED U937 CELLS

During the course of serious bacterial infections, lipopolysaccharide (LPS) interacts with monocyte/macrophage receptors, resulting in the g eneration of inflammatory cytokines. Transcription factor NF-kappa B i s crucial in activating the transcription of genes encoding proinflamm atory cytokines. In this paper, we demonstrate that the activation of NF-kappa B by LPS in a promonocytic cell line (U937) followed a rather slow kinetics, depending on the rate of I kappa B-alpha inhibitor hyd rolysis. No degradation of p105 and p100 inhibitors was observed under these conditions. The transduction pathway leading to NF-kappa B acti vation in U937 cells involved the intracellular generation of reactive oxygen species (ROS), as demonstrated by the concomitant inhibitory e ffects of antioxidants on NF-kappa B activation and the emission of a fluorescent probe reacting intracellularly with hydrogen peroxide. Thi s ROS pathway was also characterized by the use of other inhibitors. T his finding indicates that phospholipase A2 and 5-lipoxygenase are als o involved. However, the NF-kappa B activation pathway involving the a cidic sphingomyelinase of the endolysosomial membrane did not seem to participate in the LPS-induced NF-kappa B activation in U937 cells. Co pyright (C) 1997 Elsevier Science Inc.