Pulsatile Stimulation Determines Timing and Specificity of NF-κB-Dependent Transcription

摘要: The nuclear factor kappa B (NF-kappa B) transcription regulates cellular stress responses and the immune response to infection. NF-kappa activation results in oscillations abundance. To define function of these oscillations, we treated cells with repeated short pulses tumor necrosis factor-alpha at various intervals mimic pulsatile inflammatory signals. At all pulse that were analyzed, observed synchronous cycles translocation. Lower frequency stimulations gave full-amplitude translocations, whereas higher reduced translocation, indicating a failure reset. Deterministic stochastic mathematical models predicted how negative feedback loops regulate both resetting system heterogeneity. Altering stimulation different patterns B-dependent gene expression, which supports idea oscillation has functional role.