Selectivity of the NF-κB Response

NF-kappa B is activated by many stimuli and NF-kappa B binding sites have been identified in a wide variety of genes. Yet, NF-kappa B-dependent gene expression must be stimulus- and cell-type-specific. In others words, the cellular response to different NF-kappa B activating stimuli, such as TNF alpha, IL-1, and LPS, must be different; and the response of different cell types, such as lymphocytes, fibroblasts, or epithelial cells, to the same NF-kappa B-inducing stimulus must also be different. Finally, kinetics of gene expression must be accounted for, so that all NF-kappa B-dependent genes are not activated simultaneously even if cell type and stimulus are constant. Here, we explore the mechanistic framework in which such regulatory aspects of NF-kappa B-dependent gene expression have been analyzed because they are likely to form the basis for physiological responses.