Sci. Signal., 14 January 2014
Rewiring NF-B SignalingThe bacterial product lipopolysaccharide (LPS) stimulates nuclear factor B (NF-B) signaling, which results in the production of proinflammatory cytokines, such as tumor necrosis factor–α (TNF-α), as part of the immune response. NF-B target genes also include those encoding proteins that inhibit NF-B signaling through negative feedback loops. By simultaneously studying the dynamics of the nuclear translocation of the NF-B subunit RelA and the activity of a Tnf-driven reporter in a mouse macrophage cell line, Sung et al. found that the gene encoding RelA was also a target of NF-B. Synthesis of RelA occurred only at higher concentrations of LPS and constituted a positive feedback loop that dominated over existing negative feedback mechanisms. Genes expressed in response to a high concentration of LPS were enriched for those involved in innate immune responses. Together, these data suggest that the RelA-mediated positive feedback loop enables macrophages to mount an effective immune response only above a critical concentration of LPS.
Citation: M.-H. Sung, N. Li, Q. Lao, R. A. Gottschalk, G. L. Hager, I. D. C. Fraser, Switching of the Relative Dominance Between Feedback Mechanisms in Lipopolysaccharide-Induced NF-B Signaling. Sci. Signal. 7, ra6 (2014).
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