Celecoxib Exerts a Therapeutic Effect Against Demyelination by Improving the Immune and Inflammatory Microenvironments
| Autor: | Jianlin Cui, Yuhao Li, Hao Zhang, Huiling Meng, Yajia Cheng, Peipei Cao, Haiqi Xu, Siwen Zang, Zongjin Li |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microglia biology medicine.diagnostic_test business.industry Regeneration (biology) Immunology biology.organism_classification 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Immune system Western blot Apoptosis 030220 oncology & carcinogenesis Cancer research medicine Celecoxib Immunology and Allergy Remyelination business Zebrafish medicine.drug |
| Zdroj: | Journal of Inflammation Research. 13:1043-1055 |
| ISSN: | 1178-7031 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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