Achieving stability of lipopolysaccharide-induced NF-kappaB activation - PubMed (original) (raw)

. 2005 Sep 16;309(5742):1854-7.

doi: 10.1126/science.1112304.

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Achieving stability of lipopolysaccharide-induced NF-kappaB activation

Markus W Covert et al. Science. 2005.

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Abstract

The activation dynamics of the transcription factor NF-kappaB exhibit damped oscillatory behavior when cells are stimulated by tumor necrosis factor-alpha (TNFalpha) but stable behavior when stimulated by lipopolysaccharide (LPS). LPS binding to Toll-like receptor 4 (TLR4) causes activation of NF-kappaB that requires two downstream pathways, each of which when isolated exhibits damped oscillatory behavior. Computational modeling of the two TLR4-dependent signaling pathways suggests that one pathway requires a time delay to establish early anti-phase activation of NF-kappaB by the two pathways. The MyD88-independent pathway required Inferon regulatory factor 3-dependent expression of TNFalpha to activate NF-kappaB, and the time required for TNFalpha synthesis established the delay.

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