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

Proceedings of the National Academy of Sciences of the United States of America
Claire V HarperMichael R H White

Abstract

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.

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Citations

Mar 1, 2019·Scandinavian Journal of Public Health·Konstantinos Voskarides
Aug 4, 2020·PLoS Computational Biology·Giorgos MinasDavid A Rand
Jan 9, 2019·Frontiers in Immunology·Rachel H Nelson, David E Nelson
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Feb 1, 2020·Scientific Reports·Marcel JentschAlexander Loewer
May 2, 2019·Frontiers in Immunology·Ning SongLinlin Guo
Jan 19, 2019·Scientific Reports·Faisal MinshawiStamatia Papoutsopoulou
Sep 23, 2020·Disease Models & Mechanisms·Katie LloydUNKNOWN SysmedIBD Consortium
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Apr 1, 2021·Journal of Biomedical Nanotechnology·Bin ZhangHuashi Guan
May 29, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Ke XueChunlei Zhu
Jul 22, 2021·Journal of the American Chemical Society·Ke XueBen Zhong Tang

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Datasets Mentioned

BETA
E-MTAB-5158

Methods Mentioned

BETA
confocal microscopy
ChIP
transfection
PCR

Software Mentioned

Cell Tracker
Nimblescan

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