PMID- 29760065 OWN - NLM STAT- MEDLINE DCOM- 20180904 LR - 20220129 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 115 IP - 22 DP - 2018 May 29 TI - Temperature regulates NF-kappaB dynamics and function through timing of A20 transcription. PG - E5243-E5249 LID - 10.1073/pnas.1803609115 [doi] AB - NF-kappaB signaling plays a pivotal role in control of the inflammatory response. We investigated how the dynamics and function of NF-kappaB were affected by temperature within the mammalian physiological range (34 degrees C to 40 degrees C). An increase in temperature led to an increase in NF-kappaB nuclear/cytoplasmic oscillation frequency following Tumor Necrosis Factor alpha (TNFalpha) 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-kappaB 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 TNFalpha-regulated genes were implicated in NF-kappaB cross-talk with key cell-fate-controlling pathways. In conclusion, NF-kappaB dynamics and target gene expression are modulated by temperature and can accurately transmit multidimensional information to control inflammation. CI - Copyright (c) 2018 the Author(s). Published by PNAS. FAU - Harper, C V AU - Harper CV AD - 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. FAU - Woodcock, D J AU - Woodcock DJ AD - Mathematics Institute, University of Warwick, CV4 7AL Coventry, United Kingdom. AD - Zeeman Institute for Systems Biology and Infectious Epidemiology Research, University of Warwick, CV4 7AL Coventry, United Kingdom. FAU - Lam, C AU - Lam C AD - 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. FAU - Garcia-Albornoz, M AU - Garcia-Albornoz M AD - 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. FAU - Adamson, A AU - Adamson A AUID- ORCID: 0000-0002-5408-0013 AD - 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. FAU - Ashall, L AU - Ashall L AD - 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. FAU - Rowe, W AU - Rowe W AD - 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. FAU - Downton, P AU - Downton P AD - 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. FAU - Schmidt, L AU - Schmidt L AD - 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. FAU - West, S AU - West S AD - Institute of Integrative Biology, University of Liverpool, L69 7ZB United Kingdom. FAU - Spiller, D G AU - Spiller DG AD - 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. FAU - Rand, D A AU - Rand DA AD - Mathematics Institute, University of Warwick, CV4 7AL Coventry, United Kingdom; david.rand@warwick.ac.uk mike.white@manchester.ac.uk. AD - Zeeman Institute for Systems Biology and Infectious Epidemiology Research, University of Warwick, CV4 7AL Coventry, United Kingdom. FAU - White, M R H AU - White MRH AUID- ORCID: 0000-0002-3617-3232 AD - 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. LA - eng GR - BBF0059382/BB/F0059381/BBF00561X1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BB/F529003/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BB/F005814/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BB/F005938/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BB/K003097/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - MR/M008908/1/MRC_/Medical Research Council/United Kingdom GR - MR/K015885/1/MRC_/Medical Research Council/United Kingdom GR - BB/F005318/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180514 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.19.12 (TNFAIP3 protein, human) RN - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3) RN - EC 3.4.22.- (Tnfaip3 protein, mouse) SB - IM MH - Animals MH - Cell Line, Tumor MH - Cells, Cultured MH - Cytokines/metabolism MH - Gene Expression Regulation/genetics/*physiology MH - Gene Knockdown Techniques MH - Humans MH - Inflammation MH - Mice MH - NF-kappa B/genetics/*metabolism MH - Signal Transduction/genetics/physiology MH - Temperature MH - Tumor Necrosis Factor alpha-Induced Protein 3/analysis/genetics/*metabolism MH - Tumor Necrosis Factor-alpha/*metabolism PMC - PMC5984538 OTO - NOTNLM OT - A20 OT - NF-kappaB OT - dynamics OT - temperature OT - transcription COIS- The authors declare no conflict of interest. EDAT- 2018/05/16 06:00 MHDA- 2018/09/05 06:00 PMCR- 2018/05/14 CRDT- 2018/05/16 06:00 PHST- 2018/05/16 06:00 [pubmed] PHST- 2018/09/05 06:00 [medline] PHST- 2018/05/16 06:00 [entrez] PHST- 2018/05/14 00:00 [pmc-release] AID - 1803609115 [pii] AID - 201803609 [pii] AID - 10.1073/pnas.1803609115 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2018 May 29;115(22):E5243-E5249. doi: 10.1073/pnas.1803609115. Epub 2018 May 14.