INTERLEUKIN-1-BETA INDUCES NUCLEAR FACTOR KAPPA-B IN EPITHELIAL-CELLSINDEPENDENTLY OF THE PRODUCTION OF REACTIVE OXYGEN INTERMEDIATES

A large body of work has been devoted to tumor necrosis factor alpha o r interleukin-1 beta (IL-1 beta) signaling leading to the activation o f the transcription factor nuclear factor-kappa B (NF-kappa B) in vari ous cell types. Several studies have indicated that NF-kappa B activat ion depends strictly on the production of reactive oxygen intermediate s. In this report, we first demonstrated that IL-1 beta is a potent ac tivator of NF-kappa B in various epithelial transformed cell lines (OV CAR-3, SKOV-3, MCF7 A/Z). In these cells, IL-1 beta rapidly induces NF -kappa B through a complete degradation of I kappa B-alpha, while H2O2 activates NF-kappa B with slower kinetics through a partial degradati on of I kappa B-alpha, p100 and p105. We showed that IL-1 beta-mediate d induction of NF-kappa B in OVCAR-3 and in other epithelial cell line s does not proceed through the production of reactive oxygen intermedi ates, while the same cytokine activates NF-kappa B in lymphoid cells t hrough the intracellular generation of H2O2. Our study demonstrated th at several signaling pathways lead to the activation of NF-kappa B, fo llowing IL-1 beta treatment in different cell types.