Please use this identifier to cite or link to this item:
doi:10.22028/D291-40391
Title: | The Microtubule-Targeting Agent Pretubulysin Impairs the Inflammatory Response in Endothelial Cells by a JNK-Dependent Deregulation of the Histone Acetyltransferase Brd4 |
Author(s): | Primke, Tobias F. Ingelfinger, Rebecca Elewa, Mohammed A. F. Macinkovic, Igor Weigert, Andreas Fabritius, Matthias P. Reichel, Christoph A. Ullrich, Angelika Kazmaier, Uli Burgers, Luisa D. Fürst, Robert |
Language: | English |
Title: | Cells |
Volume: | 12 |
Issue: | 16 |
Publisher/Platform: | MDPI |
Year of Publication: | 2023 |
Free key words: | inflammation endothelium leukocyte adhesion cascade cell adhesion molecules microtubule-targeting agents c-jun-N-terminal kinase NFκB bromodomain-containing protein 4 |
DDC notations: | 500 Science |
Publikation type: | Journal Article |
Abstract: | The anti-inflammatory effects of depolymerizing microtubule-targeting agents on leukocytes are known for a long time, but the potential involvement of the vascular endothelium and the underlying mechanistic basis is still largely unclear. Using the recently synthesized depolymerizing microtubule-targeting agent pretubulysin, we investigated the antiinflammatory potential of pretubulysin and other microtubule-targeting agents with respect to the TNF-induced leukocyte adhesion cascade in endothelial cells, to improve our understanding of the underlying biomolecular background. We found that treatment with pretubulysin reduces inflammation in vivo and in vitro via inhibition of the TNF-induced adhesion of leukocytes to the vascular endothelium by down-regulation of the pro-inflammatory cell adhesion molecules ICAM-1 and VCAM-1 in a JNK-dependent manner. The underlying mechanism includes JNK-induced deregulation and degradation of the histone acetyltransferase Bromodomaincontaining protein 4. This study shows that depolymerizing microtubule-targeting agents, in addition to their established effects on leukocytes, also significantly decrease the inflammatory activation of vascular endothelial cells. These effects are not based on altered pro-inflammatory signaling cascades, but require deregulation of the capability of cells to enter constructive transcription for some genes, setting a baseline for further research on the prominent antiinflammatory effects of depolymerizing microtubule-targeting agents. |
DOI of the first publication: | 10.3390/cells12162112 |
URL of the first publication: | https://doi.org/10.3390/cells12162112 |
Link to this record: | urn:nbn:de:bsz:291--ds-403913 hdl:20.500.11880/36312 http://dx.doi.org/10.22028/D291-40391 |
ISSN: | 2073-4409 |
Date of registration: | 28-Aug-2023 |
Description of the related object: | Supplementary Materials |
Related object: | https://www.mdpi.com/article/10.3390/cells12162112/s1 |
Faculty: | NT - Naturwissenschaftlich- Technische Fakultät |
Department: | NT - Chemie |
Professorship: | NT - Prof. Dr. Uli Kazmaier |
Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Files for this record:
File | Description | Size | Format | |
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cells-12-02112-v2.pdf | 4,43 MB | Adobe PDF | View/Open |
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