Role of the NF-κB system in context-specific tuning of the inflammatory gene response. (February 2021)

• Record Type: Journal Article
• Authors: Chawla, Meenakshi; Roy, Payel; Basak, Soumen
• Is Part Of: Current opinion in immunology. Volume 68(2021)
• Page Start: 21
• Page End: 27
• Publication Date: 2021-02
• Subjects: Immunology -- Periodicals; Allergy -- Periodicals; Immunology -- Abstracts -- Periodicals; Allergy -- Abstracts -- Periodicals; 616.079
• DOI: 10.1016/j.coi.2020.08.005
• Languages: English
• ISSNs: 0952-7915

Abstract

Highlights: Inflammatory genes are activated in a stimulus-type-specific and cell-type-specific manner. Deregulated inflammatory gene expressions have been linked to human ailments. Mainly RelA:p50, induced by the canonical NF-κB pathway, activates inflammatory genes. Activation dynamics of RelA:p50 instructs context-specific inflammatory gene patterns. Context-specific induction of other NF-κB factors also tune inflammatory genes. Abstract : The canonical NF-κB 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-κB 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-κB complexes cumulatively instruct context-specific inflammatory gene patterns. We propose that integrating mechanistic knowledge and systems-level analyses may offer further insights on NF-κB-mediated inflammatory gene control in the future.