Unknown

Dataset Information

0

Macrophage-Specific NF-?B Activation Dynamics Can Segregate Inflammatory Bowel Disease Patients.


ABSTRACT: 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 frozen peripheral blood mononuclear cell samples. Following activation, samples could be segregated into three clusters based on the NF-?B-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-?B-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-?B 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-?B 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.

SUBMITTER: Papoutsopoulou S 

PROVIDER: S-EPMC6749845 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

altmetric image

Publications


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. T  ...[more]

Similar Datasets

| S-EPMC3020373 | biostudies-literature
| S-EPMC9234609 | biostudies-literature
2009-08-11 | GSE12434 | GEO
| S-EPMC8309978 | biostudies-literature
| S-EPMC6885517 | biostudies-literature
| S-EPMC6776398 | biostudies-literature
2011-11-12 | E-GEOD-23421 | biostudies-arrayexpress
| PRJNA943357 | ENA
| S-EPMC4815975 | biostudies-other
| S-EPMC7294995 | biostudies-literature