Hazel England

Overexpression of IκB⍺ modulates NF-κB activation of inflammatory target gene expression

Polly Downton, James Bagnall, Hazel England, David G. Spiller et autres

Cells respond to inflammatory stimuli such as cytokines by activation of the nuclear factor-κB (NF-κB) signalling pathway, resulting in oscillatory translocation of the transcription factor p65 between nucleus and cytoplasm in some cell types. We investigate the relationship between p65 and inhibitor-κB⍺ …

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Overexpression of IκBα modulates NF-κB activation of inflammatory target gene expression

Polly Downton, James Bagnall, Hazel England, David G. Spiller et autres

Abstract Cells respond to inflammatory stimuli such as cytokines by activation of the nuclear factor-κB (NF-κB) signalling pathway, resulting in oscillatory translocation of the transcription factor p65 between nucleus and cytoplasm to mediate immune response. We investigate the relationship between p65 and …

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Effects of Human RelA Transgene on Murine Macrophage Inflammatory Responses

Stamatia Papoutsopoulou, Lorna Morris, Andrew Bayliff, Thomas Mair et autres

The NFκB transcription factors are major regulators of innate immune responses, and NFκB signal pathway dysregulation is linked to inflammatory disease. Here, we utilised bone marrow-derived macrophages from the p65-DsRedxp/IκBα-eGFP transgenic strain to study the functional implication of xenogeneic (human) RelA(p65) protein …

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Using systems medicine to identify a therapeutic agent with potential for repurposing in inflammatory bowel disease

Katie Lloyd, Stamatia Papoutsopoulou, Emily Smith, Philip Stegmaier et autres

ABSTRACT Inflammatory bowel diseases (IBDs) cause significant morbidity and mortality. Aberrant NF-κB signalling is strongly associated with these conditions, and several established drugs influence the NF-κB signalling network to exert their effect. This study aimed to identify drugs that alter NF-κB signalling …

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Gene-Specific Linear Trends Constrain Transcriptional Variability of the Toll-like Receptor Signaling

James Bagnall, William Rowe, Nissrin Alachkar, James K. Roberts et autres

Single-cell gene expression is inherently variable, but how this variability is controlled in response to stimulation remains unclear. Here, we use single-cell RNA-seq and single-molecule mRNA counting (smFISH) to study inducible gene expression in the immune toll-like receptor system. We show that …

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Macrophage-Specific NF-κB Activation Dynamics Can Segregate Inflammatory Bowel Disease Patients

Stamatia Papoutsopoulou, Michael D. Burkitt, François Bergey, Hazel England et autres

The heterogeneous nature of inflammatory bowel disease (IBD) presents challenges, particularly when choosing therapy. Activation of the NF-B transcription factor is a highly regulated, dynamic event in IBD pathogenesis. Using a lentivirus approach, NF-B-regulated luciferase was expressed in patient macrophages, isolated from …

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Macrophage-specific NF-κB activation dynamics can segregate inflammatory bowel disease patients

Stamatia Papoutsopoulou, Michael D. Burkitt, François Bergey, Hazel England et autres

Abstract The heterogeneous nature of inflammatory bowel disease (IBD) presents challenges, particularly when choosing therapy. Activation of the NF-κB transcription factor is a highly-regulated, dynamic event in IBD pathogenesis. We expressed the human NF-κB/p65 subunit in blood-derived macrophages, using lentivirus. Confocal imaging …

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Using systems medicine to identify a therapeutic agent with potential for repurposing in Inflammatory Bowel Disease

Katie Lloyd, Stamatia Papoutsopoulou, Emily Smith, Philip Stegmaier et autres

Abstract Objective Inflammatory bowel diseases cause significant morbidity and mortality. Aberrant NF-κB signalling is strongly associated with these conditions, and several established drugs influence the NF-κB signalling network to exert their effect. This study aimed to identify drugs which alter NF-κB signalling …

gb, de, ru (code pays fourni par la source)

Quantitative analysis of competitive cytokine signaling predicts tissue thresholds for the propagation of macrophage activation

James Bagnall, Christopher Boddington, Hazel England, Ruth Brignall et autres

transcriptional response correlated with the extent of NF-κB signaling in the cells and their size. We compared the rates of TNF-α production and uptake in macrophages and mouse embryonic fibroblasts and generated a mathematical model to explore the heterogeneity in the response …

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Boron-Based Inhibitors of the NLRP3 Inflammasome

Alex G. Baldwin, Jack Rivers‐Auty, Michael J. Daniels, Claire White et autres

NLRP3 is a receptor important for host responses to infection, yet is also known to contribute to devastating diseases such as Alzheimer's disease, diabetes, atherosclerosis, and others, making inhibitors for NLRP3 sought after. One of the inhibitors currently in use is 2-aminoethoxy …

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Integration of Kinase and Calcium Signaling at the Level of Chromatin Underlies Inducible Gene Activation in T Cells

Ruth Brignall, Pierre Cauchy, Sarah L. Bevington, Bethany Gorman et autres

TCR signaling pathways cooperate to activate the inducible transcription factors NF-κB, NFAT, and AP-1. In this study, using the calcium ionophore ionomycin and/or PMA on Jurkat T cells, we show that the gene expression program associated with activation of TCR signaling is …

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CCDC 1563192: Experimental Crystal Structure Determination

Alex G. Baldwin, Jack Rivers‐Auty, Michael J. Daniels, Claire White et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …