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

Harper, Claire V.; Woodcock, Dan J.; Lam, Connie W.; Garcia-Albornoz, Manuel; Adamson, Antony; Ashall, Louise; Rowe, William; Downton, Polly; Schmidt, Lorraine; West, Simon; Spiller, David G.; Rand, D.A.J.; White, Michael R. H.

doi:10.1073/pnas.1803609115

Cited by 51 publications

(69 citation statements)

References 33 publications

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“…S8). This analysis also revealed a role in temperature regulation for the A20 protein feedback acting via IKK on temperature sensitivity in line with previous reports (Harper et al, 2018).…”

Section: Nf-κb Sensitivity To Hs Temperatures Are Cytokine Specificsupporting

confidence: 92%

“…Several lines of evidence highlight the modulation of IKK signalosome and the concurrent HSF1-HSP feedback activation as the key regulators of responses to elevated temperature (Esquivel-Velazquez et al, 2015;Janus et al, 2015;Kardynska et al, 2018;Lee et al, 2004;Lee et al, 2005;Morimoto, 1998;Perkins, 2004;Wong et al, 1997b). It is thought that 1 4 physiological temperatures (<40°C) modulate IKK and consequently fine-tune NF-κB responses (oscillations) via the timing of the A20 negative feedback (Harper et al, 2018). In contrast, responses to extreme temperatures (>40°C) have been shown to involve direct attenuation of IKK activity via temperature-dependent denaturation and loss of solubility (Kardynska et al, 2018;Lee et al, 2004;Pittet et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…After 4h recovery, almost 90% of cells exhibited at least five nuclear translocations (and 50% after 2h recovery) within 10h after cytokine treatment. This is indicative of HS-mediated response modulation (Harper et al, 2018).…”

Section: Hs Modulates the Nf-κb Signalling Responses To Tnfα Stimulationmentioning

confidence: 94%

“…However, a better understanding of the temperature effect on cellular signalling, in general, and crosstalk between HSR and NF-κB systems, in particular, is required for better efficacy. The NF-κB system can adapt to physiological (<40°C) temperatures (Harper et al, 2018), but exposure to higher temperatures (>40°C) results in the attenuation of the NF-κB signalling and function (Esquivel-Velazquez et al, 2015;Janus et al, 2015;Kardynska et al, 2018;Wong et al, 1997b). This involves IKK denaturation (Kardynska et al, 2018;Lee et al, 2004;Pittet et al, 2005), with inhibition of IκB degradation, NF-κB phosphorylation and translocation as well as target gene expression (Ayad et al, 1998;Cooper et al, 2010;Feinstein et al, 1997;Furuta et al, 2004;Janus et al, 2015;Wong et al, 1997a, b).…”

Section: Introductionmentioning

confidence: 99%

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Heat shock response pathways regulate stimulus-specificity and sensitivity of NF-κB signalling to temperature stress

Paszek

Kardyńska

Bagnall

et al. 2019

Preprint

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Ability to adapt to temperature changes trough the Heat Shock Response (HSR) pathways is one of the most fundamental and clinically relevant cellular response systems. Here we report that Heat Shock (HS) induces a temporally-coordinated and stimulus-specific adaptation of the signalling and gene expression responses of the Nuclear Factor κ B (NF-κB) transcription factor. We show that exposure of MCF7 breast adenocarcinoma cells to 43°C 1h HS inhibits the immediate signalling response to pro-inflammatory Interleukin 1β (IL1β) and Tumour Necrosis Factor α (TNFα) cytokines. Within 4h after HS treatment IL1β-induced responses return to normal levels, but the recovery of the TNFα-induced responses is delayed. Using siRNA knock-down of Heat Shock Factor 1 and mathematical modelling we show that the stimulus-specificity is conferred via the Inhibitory κ B kinase signalosome, with HSR differentially controlling individual cytokine transduction pathways. Finally, using a novel mathematical model we predict and experimentally validate that the HSR cross-talk confers differential cytokine sensitivity of the NF-κB system to a range of physiological and clinically-relevant temperatures. This quantitative understanding of NF-κB and HSR crosstalk mechanisms is fundamentally important for the potential improvement of current hyperthermia protocols.

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Section: Nf-κb Sensitivity To Hs Temperatures Are Cytokine Specificsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Hs Modulates the Nf-κb Signalling Responses To Tnfα Stimulationmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Heat shock response pathways regulate stimulus-specificity and sensitivity of NF-κB signalling to temperature stress

Paszek

Kardyńska

Bagnall

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…1(a)) to regulate gene transcription of more than 500 genes in a highly versatile way [8,10]. NF-κB regulates cell fate and inflammatory signalling in response to diverse stimuli, including changes in temperature [9], viral and bacterial pathogens, free radicals, cytokines, and growth factors [10]. Thus, we have a situation where both the input signal S that encodes information about the cell's environment, and the gene response R are multi-dimensional.…”

Section: Introductionmentioning

confidence: 99%

Multiplexing information flow through dynamic signalling systems

Minas

Woodcock

Ashall

et al. 2019

Preprint

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We provide experimental evidence suggesting that the NF-κB transcription factor can multiplex information about changes in multiple signals in the sense that the NF-κB target genes response can identify which of these signals have changed. In view of this, we consider how a signalling system can act as an information hub by multiplexing multiple signals. We formally define multiplexing, mathematically characterise which systems can multiplex and how well they can do it. We believe this may resolve the apparent paradox of how a system like NF-κB that regulates cell fate and inflammatory signalling in response to diverse stimuli can appear to have the low information carrying capacity suggested by recent studies on scalar signals. In carrying out our study, we introduce new methods for the analysis of large, nonlinear stochastic dynamic models, and develop computational algorithms that facilitate the calculation of fundamental constructs of information theory such as Kullback-Leibler divergences and sensitivity matrices, and link these methods to new theory about multiplexing information. We show that many current models such as those of the NF-κB system cannot multiplex effectively and provide models that overcome this limitation using post-transcriptional modifications.

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Microfluidic Construction of Responsive Photonic Microcapsules of Cholesteric Liquid Crystal for Colorimetric Temperature Microsensors

Pan

Xie

Wang

et al. 2022

Advanced Optical Materials

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It plays a critical role in various physiological activities and pathological states of organisms, including gene expression, cell division and inflammatory responses. [2] Monitoring the temperature on the micro/nano-scale is of major fundamental interest for a wide range of disciplines, ranging from biological processes, [3] chemical reactions, [4] micro/nano-electronics, [5] and micro/ nano-fluidics. [6] Currently, temperature microsensors are mainly thermocouples, [7] thermistors [8] and luminescence thermometers. [9] Thermocouples and thermistors are realized based on electrical properties with great stability and reliability; however, their structural features and uncertain material cytotoxicity may cause damage to cells. [7,8] Luminescence thermometer with small size and high sensitivity is an excellent candidate for measuring temperature. However, the fabrication of such systems depends on special chemical reagents and miscellaneous steps, leading to poor biocompatibility. [9c] Therefore, it is still a challenge to fabricate a temperature sensor with good stability and biocompatibility.Colorimetric temperature microsensors hold advantages of simple usage and direct read. In the class of colorimetric materials, cholesteric liquid crystal (CLC) possesses the advantages of quick response, and reversible and adjustable color range, [10] which have shown great potential for As alternatives to electronic devices, optically active structures from responsive nanomaterials offer great opportunity for building up smart functional sensors. This work reports on the construction and application of photonic microcapsules (PMCs) for colorimetric temperature microsensors, enabling miniaturization for injectable local micro-area sensing and integration for large-area sensing. Monodispersed PMCs are produced by in situ photopolymerization of hydrogel shells of cholesteric liquid crystal (CLC)-in-waterin-oil double emulsion droplets prepared using microfluidic devices, with controllable physical structures and chemical compositions. Constructed PMCs exhibit thermal responsive structural color according to the selective Bragg reflection of CLC's periodical helical structures within the microdroplet's spherical confinement. CLC mixtures with phase transition temperature of 56.0 and 37.8 °C have been prepared and employed to construct PMCs exhibiting obviously visible and quantifiable optical response in 52-56 and 33-38 °C, respectively. The PMCs have been successfully applied for monitoring the living cell extracellular temperature via co-incubation with cell suspension, and for sensing human forehead temperature via a flexible device from assembled PMCs. These PMCs can be flexibly applied in either micro-environment or large-area surface, enabling wide applications for a precision temperature monitoring of biological activities (e.g., cells or organs), optoelectronic devices working conditions (e.g., temperature indicators under extreme conditions), etc.

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

Cited by 51 publications

References 33 publications

Heat shock response pathways regulate stimulus-specificity and sensitivity of NF-κB signalling to temperature stress

Heat shock response pathways regulate stimulus-specificity and sensitivity of NF-κB signalling to temperature stress

Multiplexing information flow through dynamic signalling systems

Microfluidic Construction of Responsive Photonic Microcapsules of Cholesteric Liquid Crystal for Colorimetric Temperature Microsensors

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