Editors' ChoiceImmunology

Temporal Controls in Inflammatory Responses

Science's STKE  20 Sep 2005:
Vol. 2005, Issue 302, pp. tw335
DOI: 10.1126/stke.3022005tw335

Understanding control of cellular regulation requires not only a description of the signaling events and mediators involved but also an understanding of the temporal properties of how signals are generated and sensed. Covert et al. and Werner et al. now provide insight into temporal control of signals that control the activity of a key mediator of inflammatory responses, the transcription factor NF-κB. Signals from the receptor for the inflammatory cytokine tumor necrosis factor or from the Toll-like receptor 4 (TLR4), which recognizes bacterial lipopolysaccharide, result in either oscillating or stable patterns of NF-κB activity, respectively, which in turn lead to distinct patterns of gene expression. Computational models and biochemical analysis reveal the regulatory events that produce the distinct temporal patterns of NF-κB activity. The stable signal produced by activation of TLR4 appears to result from activation of two signaling pathways--a rapid one and a slower one that requires protein synthesis and autocrine signaling.

M. W. Covert, T. H. Leung, J. E. Gaston, D. Baltimore, Achieving stability of lipopolysaccharide-induced NF-κB activation. Science 309, 1854-1857 (2005). [Abstract] [Full Text]

S. L. Werner, D. Barken, A. Hoffmann, Stimulus specificity of gene expression programs determined by temporal control of IKK activity. Science 309, 1857-1861 (2005). [Abstract] [Full Text]