Celecoxib Exerts a Therapeutic Effect Against Demyelination by Improving the Immune and Inflammatory Microenvironments

Peipei Cao,1 Hao Zhang,2 Huiling Meng,1 Yajia Cheng,1 Haiqi Xu,3 Siwen Zang,1 Zongjin Li,1 Jianlin Cui,1,4 Yuhao Li1,5 1Nankai University School of Medicine, Tianjin, People’s Republic of China; 2Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People&r...

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Autores principales:	Cao P, Zhang H, Meng H, Cheng Y, Xu H, Zang S, Li Z, Cui J, Li Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	celecoxib demyelination oligodendrocytes remyelination zebrafish Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/94715a399b7c4aae8936528167f77846
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spelling	oai:doaj.org-article:94715a399b7c4aae8936528167f778462021-12-02T14:50:24ZCelecoxib Exerts a Therapeutic Effect Against Demyelination by Improving the Immune and Inflammatory Microenvironments1178-7031https://doaj.org/article/94715a399b7c4aae8936528167f778462020-12-01T00:00:00Zhttps://www.dovepress.com/celecoxib-exerts-a-therapeutic-effect-against-demyelination-by-improvi-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Peipei Cao,1 Hao Zhang,2 Huiling Meng,1 Yajia Cheng,1 Haiqi Xu,3 Siwen Zang,1 Zongjin Li,1 Jianlin Cui,1,4 Yuhao Li1,5 1Nankai University School of Medicine, Tianjin, People’s Republic of China; 2Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 3Faculty of Life Science, University of Liverpool, Liverpool, UK; 4Medical International Collaborative Innovation Center, Nankai University School of Medicine, Tianjin, People’s Republic of China; 5Department of Pathology, Nankai University School of Medicine, Tianjin, People’s Republic of ChinaCorrespondence: Yuhao LiDepartment of Pathology, Nankai University School of Medicine, 94 Weijin Road, Tianjin 300071, People’s Republic of ChinaTel +86 22 23502554Email liyuhao@nankai.edu.cnJianlin CuiMedical International Collaborative Innovation Center, Nankai University School of Medicine, 94 Weijin Road, Tianjin 300071, People’s Republic of ChinaTel +86 22 23502554Email cuijianlin@nankai.edu.cnBackground: 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.Keywords: celecoxib, demyelination, oligodendrocytes, remyelination, zebrafishCao PZhang HMeng HCheng YXu HZang SLi ZCui JLi YDove Medical PressarticlecelecoxibdemyelinationoligodendrocytesremyelinationzebrafishPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 13, Pp 1043-1055 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	celecoxib demyelination oligodendrocytes remyelination zebrafish Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	celecoxib demyelination oligodendrocytes remyelination zebrafish Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Cao P Zhang H Meng H Cheng Y Xu H Zang S Li Z Cui J Li Y Celecoxib Exerts a Therapeutic Effect Against Demyelination by Improving the Immune and Inflammatory Microenvironments
description	Peipei Cao,1 Hao Zhang,2 Huiling Meng,1 Yajia Cheng,1 Haiqi Xu,3 Siwen Zang,1 Zongjin Li,1 Jianlin Cui,1,4 Yuhao Li1,5 1Nankai University School of Medicine, Tianjin, People’s Republic of China; 2Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 3Faculty of Life Science, University of Liverpool, Liverpool, UK; 4Medical International Collaborative Innovation Center, Nankai University School of Medicine, Tianjin, People’s Republic of China; 5Department of Pathology, Nankai University School of Medicine, Tianjin, People’s Republic of ChinaCorrespondence: Yuhao LiDepartment of Pathology, Nankai University School of Medicine, 94 Weijin Road, Tianjin 300071, People’s Republic of ChinaTel +86 22 23502554Email liyuhao@nankai.edu.cnJianlin CuiMedical International Collaborative Innovation Center, Nankai University School of Medicine, 94 Weijin Road, Tianjin 300071, People’s Republic of ChinaTel +86 22 23502554Email cuijianlin@nankai.edu.cnBackground: 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.Keywords: celecoxib, demyelination, oligodendrocytes, remyelination, zebrafish
format	article
author	Cao P Zhang H Meng H Cheng Y Xu H Zang S Li Z Cui J Li Y
author_facet	Cao P Zhang H Meng H Cheng Y Xu H Zang S Li Z Cui J Li Y
author_sort	Cao P
title	Celecoxib Exerts a Therapeutic Effect Against Demyelination by Improving the Immune and Inflammatory Microenvironments
title_short	Celecoxib Exerts a Therapeutic Effect Against Demyelination by Improving the Immune and Inflammatory Microenvironments
title_full	Celecoxib Exerts a Therapeutic Effect Against Demyelination by Improving the Immune and Inflammatory Microenvironments
title_fullStr	Celecoxib Exerts a Therapeutic Effect Against Demyelination by Improving the Immune and Inflammatory Microenvironments
title_full_unstemmed	Celecoxib Exerts a Therapeutic Effect Against Demyelination by Improving the Immune and Inflammatory Microenvironments
title_sort	celecoxib exerts a therapeutic effect against demyelination by improving the immune and inflammatory microenvironments
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/94715a399b7c4aae8936528167f77846
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_version_	1718389461072478208

Celecoxib Exerts a Therapeutic Effect Against Demyelination by Improving the Immune and Inflammatory Microenvironments

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