Nuclear Factor-kappaB: Fine-tuning a Central Integrator of Diverse Biologic Stimuli

The nuclear factor (NF)-kappa B family of proteins is a key regulator of inflammation, innate immunity, and cell survival and differentiation. Components of these pathways are potential targets of intervention for inflammation, infectious diseases, and cancer. However, therapeutic interventions that dampen the host response to infection and injury must also recognize the autoregulatory loops in the "resolution" phase of inflammation and infection. A more precise fine-tuning of these pathways leading to NF-kappaB activation will require dissecting temporally the different phases of activation and endogenous autoregulatory deactivation programs in diseases and redefining end-points after drug/inhibitor treatment to correlate changes in these stages.