NF-kappa B activation in response to toxical and therapeutical agents: role in inflammation and cancer treatment

The NF-kappaB transcription factor is ubiquitously expressed and controls t he expression of a large number of genes. Experimental data clearly indicat e that NF-kappaB is a major regulator of the inflammatory reaction by contr olling the expression of pro-inflammatory molecules in response to cytokine s, oxidative stress and infectious agents. We demonstrated that NF-kappaB a ctivation by IL-1 beta follows three distinct cell-specific pathways. Moreo ver, our studies indicated that in one model of inflammatory diseases, hors e recurrent airway obstruction (RAO), the extent of NF-kappaB basal activit y correlates with pulmonary dysfunction. Another role of NF-kappaB activity protects cancer cells against apoptosis and could participate in the resis tance to cancer treatment. However, we did not observe any increased cytoto xicity after treatment with anticancer drugs or TNF-alpha of cells expressi ng a NF-kappaB inhibitor. Therefore, we can conclude that the inhibition of apoptosis by NF-kappaB is likely to be cell type and stimulus-dependent. F urther studies are required to determine whether NF-kappaB could be a targe t for anticancer treatments. (C) 2000 Elsevier Science Ireland Ltd. All rig hts reserved.