Temperature regulates NF-?B dynamics and function through timing of A20 transcription.

ABSTRACT: NF-?B signaling plays a pivotal role in control of the inflammatory response. We investigated how the dynamics and function of NF-?B were affected by temperature within the mammalian physiological range (34 °C to 40 °C). An increase in temperature led to an increase in NF-?B nuclear/cytoplasmic oscillation frequency following Tumor Necrosis Factor alpha (TNF?) 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-?B 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 TNF?-regulated genes were implicated in NF-?B cross-talk with key cell-fate-controlling pathways. In conclusion, NF-?B dynamics and target gene expression are modulated by temperature and can accurately transmit multidimensional information to control inflammation.

SUBMITTER: Harper CV 

PROVIDER: S-EPMC5984538 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature