Partner: Piotr Widłak


Recent publications
1.Paszek A., Kardyńska M., Bagnall J., Śmieja J., Spiller David G., Widłak P., Kimmel M., Wiesława W., Paszek P., Heat shock response regulates stimulus-specificity and sensitivity of the pro-inflammatory NF-κB signalling, Cell Communication and Signaling, ISSN: 1478-811X, DOI: 10.1186/s12964-020-00583-0, Vol.18, pp.77-1-21, 2020
Abstract:

Background

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. Heat Shock (HS) affects the signalling and gene expression responses of the Nuclear Factor κB (NF-κB) transcription factor, a critical regulator of proliferation and inflammation, however, our quantitative understanding of how cells sense and adapt to temperature changes is limited.
Methods

We used live-cell time-lapse microscopy and mathematical modelling to understand the signalling of the NF-κB system in the human MCF7 breast adenocarcinoma cells in response to pro-inflammatory Interleukin 1β (IL1β) and Tumour Necrosis Factor α (TNFα) cytokines, following exposure to a 37–43 °C range of physiological and clinical temperatures.
Results

We show that exposure to 43 °C 1 h HS inhibits the immediate NF-κB signalling response to TNFα and IL1β stimulation although uptake of cytokines is not impaired. Within 4 h after HS treatment IL1β-induced NF-κB responses return to normal levels, but the recovery of the TNFα-induced responses is still affected. Using siRNA knock-down of Heat Shock Factor 1 (HSF1) we show that this stimulus-specificity is conferred via the Inhibitory κB kinase (IKK) signalosome where HSF1-dependent feedback regulates TNFα, but not IL1β-mediated IKK recovery post HS. Furthermore, we demonstrate that through the temperature-dependent denaturation and recovery of IKK, TNFα and IL1β-mediated signalling exhibit different temperature sensitivity and adaptation to repeated HS when exposed to a 37–43 °C temperature range. Specifically, IL1β-mediated NF-κB responses are more robust to temperature changes in comparison to those induced by TNFα treatment.

Affiliations:
Paszek A.-other affiliation
Kardyńska M.-other affiliation
Bagnall J.-other affiliation
Śmieja J.-Silesian University of Technology (PL)
Spiller David G.-other affiliation
Widłak P.-other affiliation
Kimmel M.-Rice University (US)
Wiesława W.-other affiliation
Paszek P.-IPPT PAN