PUBLICATION
Celecoxib Exerts a Therapeutic Effect Against Demyelination by Improving the Immune and Inflammatory Microenvironments
- Authors
- Cao, P., Zhang, H., Meng, H., Cheng, Y., Xu, H., Zang, S., Li, Z., Cui, J., Li, Y.
- ID
- ZDB-PUB-201210-3
- Date
- 2020
- Source
- Journal of inflammation research 13: 1043-1055 (Journal)
- Registered Authors
- Cui, Jianlin, Li, Yuhao
- Keywords
- celecoxib, demyelination, oligodendrocytes, remyelination, zebrafish
- MeSH Terms
- none
- PubMed
- 33293848 Full text @ J Inflamm Res
Citation
Cao, P., Zhang, H., Meng, H., Cheng, Y., Xu, H., Zang, S., Li, Z., Cui, J., Li, Y. (2020) Celecoxib Exerts a Therapeutic Effect Against Demyelination by Improving the Immune and Inflammatory Microenvironments. Journal of inflammation research. 13:1043-1055.
Abstract
Background The myelin sheath can be damaged by genetic and/or environmental factors, leading to demyelinating diseases, for which effective treatments are lacking. Recently, cyclooxygenase-2 (COX-2) overexpression was detected in demyelinating lesions both in patients and animal models, opening an avenue for promoting endogenous remyelination. The aim of this study was to investigate the therapeutic effect of celecoxib, a selective COX-2 inhibitor, against demyelination in a zebrafish model.
Methods The biotoxicity of celecoxib was evaluated on zebrafish embryos. Metronidazole was used to deplete the oligodendrocytes in Tg (mbp:nfsB-egfp) transgenic fish. Celecoxib was then administered both in larvae and adults. The regeneration of the myelin sheath and the underlying mechanisms were explored by immunohistochemistry, flow cytometry, Western blot analysis, quantitative real-time polymerase chain reaction, and behavioral test.
Results Celecoxib had low in vivo toxicity. A stable and practical demyelination model was established by metronidazole induction. Following celecoxib treatment, the number of oligodendrocytes was increased significantly and the concentric structure of the myelin sheath reappeared. The locomotor ability was notably improved and was close to its physiological levels. The expression of arg1, mrc1, il-10, and il-4 was upregulated, while that of il-1β, il-12, tnf-α, il-6, caspase-3 and caspase-7 was downregulated.
Conclusion Inhibition of COX-2 contributed to the transformation of microglia/macrophages from the M1 to the M2 phenotype, improved the inflammatory microenvironment, and suppressed caspase-dependent apoptosis, thus exerting a therapeutic effect against demyelination.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping