scholarly journals Heat shock response regulates stimulus-specificity and sensitivity of the pro-inflammatory NF-κB signalling

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Anna Paszek ◽  
Małgorzata Kardyńska ◽  
James Bagnall ◽  
Jarosław Śmieja ◽  
David G. Spiller ◽  
...  
2019 ◽  
Author(s):  
Anna Paszek ◽  
Małgorzata Kardyńska ◽  
James Bagnall ◽  
Jarosław Śmieja ◽  
David G. Spiller ◽  
...  

AbstractAbility 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 κB (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 κB 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 cross-talk mechanisms is fundamentally important for the potential improvement of current hyperthermia protocols.


2018 ◽  
Vol 69 (2) ◽  
pp. 337-340
Author(s):  
Vlad Preluca ◽  
Bogdan Horatiu Serb ◽  
Sanda Marchian ◽  
Diter Atasie ◽  
Mihaela Cernusca Mitariu ◽  
...  

Heat shock inductors have potential as treatment for degenerative and protein misfolding diseases. Dimethyl-sulfoxide is widely used as a solvent in pharmacological screening tests and has been shown to have heat shock induction effects. Transgenic Tg (hsp70l:EGFP-HRAS_G12V)io3(AB) zebrafish larvae were exposed for 24 hours to dimethyl-sulfoxide in concentratios of 0.1-2%, and to moderate heat shock inductors pentoxifylline and tacrolimus. Positive controls were exposed to 35, 38 and 40�C for 20 min, and incubated for 24 h at 28�C. Heat shock response was measured by fluorescence microscopy and signal intensity quantification in FIJI. Dimethyl-sulfoxide caused a dose-dependant increase in fluorescent intensity, but significantly lower compared with exposure to 38 and 40�C. Pentoxifylline and tacrolimus induced a significantly higher increase in fluorescence compared with 0.5% dimethyl-sulfoxide. Thus, although dimethyl-sulfoxide has independent heat shock induction effects, concentrations of up to 0.5% are suitable for heat shock response screening tests.


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