Temperature regulates NF-κB dynamics and function through timing of A20 transcription

Proc Natl Acad Sci U S A. 2018 May 29;115(22):E5243-E5249. doi: 10.1073/pnas.1803609115. Epub 2018 May 14.


NF-κB signaling plays a pivotal role in control of the inflammatory response. We investigated how the dynamics and function of NF-κB were affected by temperature within the mammalian physiological range (34 °C to 40 °C). An increase in temperature led to an increase in NF-κB nuclear/cytoplasmic oscillation frequency following Tumor Necrosis Factor alpha (TNFα) stimulation. Mathematical modeling suggested that this temperature sensitivity might be due to an A20-dependent mechanism, and A20 silencing removed the sensitivity to increased temperature. The timing of the early response of a key set of NF-κB target genes showed strong temperature dependence. The cytokine-induced expression of many (but not all) later genes was insensitive to temperature change (suggesting that they might be functionally temperature-compensated). Moreover, a set of temperature- and TNFα-regulated genes were implicated in NF-κB cross-talk with key cell-fate-controlling pathways. In conclusion, NF-κB dynamics and target gene expression are modulated by temperature and can accurately transmit multidimensional information to control inflammation.

Keywords: A20; NF-κB; dynamics; temperature; transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cells, Cultured
  • Cytokines / metabolism
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology*
  • Gene Knockdown Techniques
  • Humans
  • Inflammation
  • Mice
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Temperature
  • Tumor Necrosis Factor alpha-Induced Protein 3 / analysis
  • Tumor Necrosis Factor alpha-Induced Protein 3 / genetics
  • Tumor Necrosis Factor alpha-Induced Protein 3 / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*


  • Cytokines
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Tnfaip3 protein, mouse