The Library
Effects of human RelA transgene on murine macrophage inflammatory responses
Tools
Tools
Tools
Papoutsopoulou, Stamatia, Morris, Lorna, Bayliff, Andrew, Mair, Thomas, England, Hazel, Stagi, Massimiliano, Bergey, François, Alam, Mohammad Tauqeer, Sheibani-Tezerji, Raheleh, Rosenstiel, Philip, Müller, Werner, Martins Dos Santos, Vitor and Campbell, Barry J. (2022) Effects of human RelA transgene on murine macrophage inflammatory responses. Biomedicines, 10 (4). e757. doi:10.3390/biomedicines10040757 ISSN 2227-9059.
|
PDF
WRAP-Effects-human-RelA-transgene-murine-macrophage-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (4061Kb) | Preview |
Official URL: https://doi.org/10.3390/biomedicines10040757
Abstract
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 introduced into the mouse genome. Confocal imaging showed that human RelA is expressed in the cells and can translocate to the nucleus following activation of Toll-like receptor 4. RNA sequencing of lipid A-stimulated macrophages, revealed that human RelA impacts on murine gene transcription, affecting both non-NFκB and NFκB target genes, including immediate-early and late response genes, e.g., Fos and Cxcl10. Validation experiments on NFκB targets revealed markedly reduced mRNA levels, but similar kinetic profiles in transgenic cells compared to wild-type. Enrichment pathway analysis of differentially expressed genes revealed interferon and cytokine signaling were affected. These immune response pathways were also affected in macrophages treated with tumor necrosis factor. Data suggests that the presence of xenogeneic RelA protein likely has inhibitory activity, altering specific transcriptional profiles of key molecules involved in immune responses. It is therefore essential that this information be taken into consideration when designing and interpreting future experiments using this transgenic strain.
| Item Type: | Journal Article | ||||||
|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QH Natural history > QH426 Genetics Q Science > QR Microbiology > QR180 Immunology R Medicine > RB Pathology |
||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||||
| SWORD Depositor: | Library Publications Router | ||||||
| Library of Congress Subject Headings (LCSH): | Genetic transcription -- Regulation, Macrophages -- Activation, Inflammation -- Mediators, Inflammation -- Immunological factors | ||||||
| Journal or Publication Title: | Biomedicines | ||||||
| Publisher: | MDPI | ||||||
| ISSN: | 2227-9059 | ||||||
| Official Date: | 24 March 2022 | ||||||
| Dates: |
|
||||||
| Volume: | 10 | ||||||
| Number: | 4 | ||||||
| Article Number: | e757 | ||||||
| DOI: | 10.3390/biomedicines10040757 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||
| Date of first compliant deposit: | 18 May 2022 | ||||||
| Date of first compliant Open Access: | 18 May 2022 | ||||||
| RIOXX Funder/Project Grant: |
|
||||||
| Related URLs: |
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
