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

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 osci...

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Main Authors: Harper, C, Woodcock, D, Lam, C, Garcia-Albornoz, M, Adamson, A, Ashall, L, Rowe, W, Downton, P, Schmidt, L, West, S, Spiller, D, Rand, D, White, M
Format: Journal article
Published: National Academy of Sciences 2018
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author Harper, C
Woodcock, D
Lam, C
Garcia-Albornoz, M
Adamson, A
Ashall, L
Rowe, W
Downton, P
Schmidt, L
West, S
Spiller, D
Rand, D
White, M
author_facet Harper, C
Woodcock, D
Lam, C
Garcia-Albornoz, M
Adamson, A
Ashall, L
Rowe, W
Downton, P
Schmidt, L
West, S
Spiller, D
Rand, D
White, M
author_sort Harper, C
collection OXFORD
description 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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spelling oxford-uuid:9398eba5-3cfa-46c1-b4f0-4b7f34a08fa82022-03-26T23:33:33ZTemperature regulates NF-κB dynamics and function through timing of A20 transcriptionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9398eba5-3cfa-46c1-b4f0-4b7f34a08fa8Symplectic Elements at OxfordNational Academy of Sciences2018Harper, CWoodcock, DLam, CGarcia-Albornoz, MAdamson, AAshall, LRowe, WDownton, PSchmidt, LWest, SSpiller, DRand, DWhite, MNF-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.
spellingShingle Harper, C
Woodcock, D
Lam, C
Garcia-Albornoz, M
Adamson, A
Ashall, L
Rowe, W
Downton, P
Schmidt, L
West, S
Spiller, D
Rand, D
White, M
Temperature regulates NF-κB dynamics and function through timing of A20 transcription
title Temperature regulates NF-κB dynamics and function through timing of A20 transcription
title_full Temperature regulates NF-κB dynamics and function through timing of A20 transcription
title_fullStr Temperature regulates NF-κB dynamics and function through timing of A20 transcription
title_full_unstemmed Temperature regulates NF-κB dynamics and function through timing of A20 transcription
title_short Temperature regulates NF-κB dynamics and function through timing of A20 transcription
title_sort temperature regulates nf κb dynamics and function through timing of a20 transcription
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