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


Papoutsopoulou, Stamatia ORCID: 0000-0001-6665-8508, Burkitt, Michael D, Bergey, Francois, England, Hazel, Hough, Rachael ORCID: 0000-0001-9765-6978, Schmidt, Lorraine, Spiller, David G, White, Michael HR, Paszek, Pawel, Jackson, Dean A et al (show 6 more authors) (2019) Macrophage-Specific NF-κB Activation Dynamics Can Segregate Inflammatory Bowel Disease Patients FRONTIERS IN IMMUNOLOGY, 10. 2168-. ISSN 1664-3224, 1664-3224

Access the full-text of this item by clicking on the Open Access link.
[thumbnail of 473700_Papoutsopoulou_Manuscript.DOCX] Other
473700_Papoutsopoulou_Manuscript.DOCX - Author Accepted Manuscript
Download (145kB)

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. Using a lentivirus approach, NF-κB-regulated luciferase was expressed in patient macrophages, isolated from frozen peripheral blood mononuclear cell samples. Following activation, samples could be segregated into three clusters based on the NF-κB-regulated luciferase response. The ulcerative colitis (UC) samples appeared only in the hypo-responsive Cluster 1, and in Cluster 2. Conversely, Crohn's disease (CD) patients appeared in all Clusters with their percentage being higher in the hyper-responsive Cluster 3. A positive correlation was seen between NF-κB-induced luciferase activity and the concentrations of cytokines released into medium from stimulated macrophages, but not with serum or biopsy cytokine levels. Confocal imaging of lentivirally-expressed p65 activation revealed that a higher proportion of macrophages from CD patients responded to endotoxin lipid A compared to controls. In contrast, cells from UC patients exhibited a shorter duration of NF-κB p65 subunit nuclear localization compared to healthy controls, and CD donors. Analysis of macrophage cytokine responses and patient metadata revealed a strong correlation between CD patients who smoked and hyper-activation of p65. These in vitro dynamic assays of NF-κB activation in blood-derived macrophages have the potential to segregate IBD patients into groups with different phenotypes and may therefore help determine response to therapy.

Item Type: Article
Uncontrolled Keywords: inflammatory bowel disease, NF-kappa B, macrophages, cytokines, Crohn's disease, ulcerative colitis
Depositing User: Symplectic Admin
Date Deposited: 24 Sep 2019 10:39
Last Modified: 16 Jun 2026 08:03
DOI: 10.3389/fimmu.2019.02168
Open Access URL: https://www.frontiersin.org/articles/10.3389/fimmu...
Related Websites:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3055744
Disclaimer: The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate.
Altmetric
CORE (COnnecting REpositories)