Research ArticleImmunology

Late-phase synthesis of IκBα insulates the TLR4-activated canonical NF-κB pathway from noncanonical NF-κB signaling in macrophages

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Science Signaling  06 Dec 2016:
Vol. 9, Issue 457, pp. ra120
DOI: 10.1126/scisignal.aaf1129

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Preventing macrophages from going haywire

Activation of the nuclear factor κB (NF-κB) transcription factors occurs through two pathways: canonical and noncanonical. In infected fibroblasts and epithelial cells, the combined activation of both pathways induces a burst of late-phase inflammatory gene expression to help eradicate pathogens. Chatterjee et al. used a combination of mathematical modeling and experiments to show that macrophages are wired differently. In macrophages, combined stimulation of canonical and noncanonical signaling led to the delayed generation of an inhibitor of the canonical pathway, thus preventing the potentially deleterious effects of excessive inflammatory responses by the macrophages. This mathematical approach may lead to the discovery of other mechanism of cell type–specific control of transcription factor activity.

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