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Título: | A cannabinoid agonist interferes with the progression of a chronic model of multiple sclerosis by downregulating adhesion molecules |
Autor: | Mestre, Leyre CSIC ORCID ; Docagne, Fabian CSIC ORCID; Correa, Fernando Gabriel CSIC; Loría, Frida CSIC ORCID; Hernangómez-Herrero, Miriam CSIC; Borrell, José CSIC; Guaza, Carmen CSIC ORCID | Palabras clave: | TMEV-IDD ICAM-1 VCAM-1 Cannabinoids Brain endothelial cells PPARγ |
Fecha de publicación: | feb-2009 | Editor: | Academic Press | Citación: | Molecular and Cellular Neurosciences 40(2): 258-266 (2009) | Resumen: | Adhesion molecules are critical players in the regulation of transmigration of blood leukocytes across the blood-brain barrier in multiple sclerosis (MS). Cannabinoids (CBs) are potential therapeutic agents in the treatment of MS, but the mechanisms involved are only partially known. Using a viral model of MS we observed that the cannabinoid agonist WIN55,212-2 administered at the time of virus infection suppresses intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in brain endothelium, together with a reduction in perivascular CD4+ T lymphocytes infiltrates and microglial responses. WIN55,212-2 also interferes with later progression of the disease by reducing symptomatology and neuroinflammation. In vitro data from brain endothelial cell cultures, provide the first evidence of a role of peroxisome proliferator-activated receptors gamma (PPARγ) in WIN55,212-2-induced downregulation of VCAM-1. This study highlights that inhibition of brain adhesion molecules by WIN55,212-2 might underline its therapeutic effects in MS models by targeting PPAR-γ receptors. © 2008 Elsevier Inc. All rights reserved. | Versión del editor: | http://doi.org/10.1016/j.mcn.2008.10.015 | URI: | http://hdl.handle.net/10261/59558 | DOI: | 10.1016/j.mcn.2008.10.015 | Identificadores: | doi: 10.1016/j.mcn.2008.10.015 issn: 1044-7431 |
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