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

Autor:	Harper CV; Systems Microscopy Centre, Division of Molecular and Cellular Function, School of Biology, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, M13 9PT Manchester, United Kingdom., Woodcock DJ; Mathematics Institute, University of Warwick, CV4 7AL Coventry, United Kingdom.; Zeeman Institute for Systems Biology and Infectious Epidemiology Research, University of Warwick, CV4 7AL Coventry, United Kingdom., Lam C; Systems Microscopy Centre, Division of Molecular and Cellular Function, School of Biology, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, M13 9PT Manchester, United Kingdom., Garcia-Albornoz M; Division of Evolution and Genomic Sciences, School of Biology, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, M13 9PT Manchester, United Kingdom., Adamson A; Systems Microscopy Centre, Division of Molecular and Cellular Function, School of Biology, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, M13 9PT Manchester, United Kingdom., Ashall L; Systems Microscopy Centre, Division of Molecular and Cellular Function, School of Biology, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, M13 9PT Manchester, United Kingdom., Rowe W; Systems Microscopy Centre, Division of Molecular and Cellular Function, School of Biology, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, M13 9PT Manchester, United Kingdom., Downton P; Systems Microscopy Centre, Division of Molecular and Cellular Function, School of Biology, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, M13 9PT Manchester, United Kingdom., Schmidt L; Systems Microscopy Centre, Division of Molecular and Cellular Function, School of Biology, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, M13 9PT Manchester, United Kingdom., West S; Institute of Integrative Biology, University of Liverpool, L69 7ZB United Kingdom., Spiller DG; Systems Microscopy Centre, Division of Molecular and Cellular Function, School of Biology, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, M13 9PT Manchester, United Kingdom., Rand DA; Mathematics Institute, University of Warwick, CV4 7AL Coventry, United Kingdom; david.rand@warwick.ac.uk mike.white@manchester.ac.uk.; Zeeman Institute for Systems Biology and Infectious Epidemiology Research, University of Warwick, CV4 7AL Coventry, United Kingdom., White MRH; Systems Microscopy Centre, Division of Molecular and Cellular Function, School of Biology, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, M13 9PT Manchester, United Kingdom; david.rand@warwick.ac.uk mike.white@manchester.ac.uk.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 May 29; Vol. 115 (22), pp. E5243-E5249. Date of Electronic Publication: 2018 May 14.
DOI:	10.1073/pnas.1803609115
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest. (Copyright © 2018 the Author(s). Published by PNAS.)
Databáze:	MEDLINE
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