Role Of The Nf-Kappa B System In Context-Specific Tuning Of The Inflammatory Gene Response

The canonical NF-kappa B pathway instructs the expression of inflammatory genes by the RelA:p50 transcription factor in response to diverse cell-activating stimuli. However, this mainstay RelA:p50 transcriptional output must also be curated so as to provide for stimulus-type-specific and cell-type-specific inflammatory responses adapted to the local tissue-microenvironment. Here, we summarize the fundamental mechanisms regulating RelA:p50-mediated gene expressions and discuss how the NF-kappa B system imparts specificity in the inflammatory gene program. We put forward a conceptual framework where the dynamical attributes and the composition of the nuclear NF-kappa B complexes cumulatively instruct context-specific inflammatory gene patterns. We propose that integrating mechanistic knowledge and systems-level analyses may offer further insights on NF-kappa B-mediated inflammatory gene control in the future.