High-affinity sigma 1 protein agonist ...
Type de document :
Article dans une revue scientifique: Article original
DOI :
PMID :
URL permanente :
Titre :
High-affinity sigma 1 protein agonist reduces clinical and pathological signs of experimental autoimmune encephalomyelitis
Auteur(s) :
Oxombre, B. [Auteur]
Lee-Chang, C. [Auteur]
Duhamel, Alain [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Toussaint, M. [Auteur]
Giroux, M. [Auteur]
Donnier-Marechal, M. [Auteur]
Carato, P. [Auteur]
Lefranc, D. [Auteur]
Zephir, H. [Auteur]
Prin, L. [Auteur]
Melnyk, Patricia [Auteur]
Vermersch, Patrick [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lee-Chang, C. [Auteur]
Duhamel, Alain [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Toussaint, M. [Auteur]
Giroux, M. [Auteur]
Donnier-Marechal, M. [Auteur]
Carato, P. [Auteur]
Lefranc, D. [Auteur]
Zephir, H. [Auteur]
Prin, L. [Auteur]
Melnyk, Patricia [Auteur]
Vermersch, Patrick [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Titre de la revue :
British journal of pharmacology
Nom court de la revue :
Br. J. Pharmacol.
Numéro :
172
Pagination :
1769-1782
Date de publication :
2015-04-01
ISSN :
0007-1188
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
OBJECTIVE: Selective agonists of the sigma-1 receptor (σ1 protein) are generally reported to protect against neuronal damage and modulate oligodendrocyte differentiation. Human and rodent lymphocytes possess saturable, ...
Lire la suite >OBJECTIVE: Selective agonists of the sigma-1 receptor (σ1 protein) are generally reported to protect against neuronal damage and modulate oligodendrocyte differentiation. Human and rodent lymphocytes possess saturable, high-affinity binding sites for compounds binding to the σ1 protein and potential immunomodulatory properties have been described for σ1 protein ligands. Experimental autoimmune encephalomyelitis (EAE) is recognized as a valuable model of the inflammatory aspects of multiple sclerosis (MS). Here, we have assessed the role of a σ1 protein agonist, containing the tetrahydroisoquinoline-hydantoin structure, in EAE. METHODS: EAE was induced in SJL/J female mice by active immunization with myelin proteolipid protein (PLP)139-151 peptide. The σ1 protein agonist was injected i.p. at the time of immunization (day 0). Disease severity was assessed clinically and by histopathological evaluation of the CNS. Phenotyping of B-cell subsets and regulatory T-cells were performed by flow cytometry in spleen and cervical lymph nodes. RESULTS: Prophylactic treatment of EAE mice with the σ1 protein agonist prevented mononuclear cell accumulation and demyelination in brain and spinal cord and increased T2 B-cells and regulatory T-cells, resulting in an overall reduction in the clinical progression of EAE. CONCLUSIONS: This σ1 protein agonist, containing the tetrahydroisoquinoline-hydantoin structure, decreased the magnitude of inflammation in EAE. This effect was associated with increased proportions of B-cell subsets and regulatory T-cells with potential immunoregulatory functions. Targeting of the σ1 protein might thus provide new therapeutic opportunities in MS.Lire moins >
Lire la suite >OBJECTIVE: Selective agonists of the sigma-1 receptor (σ1 protein) are generally reported to protect against neuronal damage and modulate oligodendrocyte differentiation. Human and rodent lymphocytes possess saturable, high-affinity binding sites for compounds binding to the σ1 protein and potential immunomodulatory properties have been described for σ1 protein ligands. Experimental autoimmune encephalomyelitis (EAE) is recognized as a valuable model of the inflammatory aspects of multiple sclerosis (MS). Here, we have assessed the role of a σ1 protein agonist, containing the tetrahydroisoquinoline-hydantoin structure, in EAE. METHODS: EAE was induced in SJL/J female mice by active immunization with myelin proteolipid protein (PLP)139-151 peptide. The σ1 protein agonist was injected i.p. at the time of immunization (day 0). Disease severity was assessed clinically and by histopathological evaluation of the CNS. Phenotyping of B-cell subsets and regulatory T-cells were performed by flow cytometry in spleen and cervical lymph nodes. RESULTS: Prophylactic treatment of EAE mice with the σ1 protein agonist prevented mononuclear cell accumulation and demyelination in brain and spinal cord and increased T2 B-cells and regulatory T-cells, resulting in an overall reduction in the clinical progression of EAE. CONCLUSIONS: This σ1 protein agonist, containing the tetrahydroisoquinoline-hydantoin structure, decreased the magnitude of inflammation in EAE. This effect was associated with increased proportions of B-cell subsets and regulatory T-cells with potential immunoregulatory functions. Targeting of the σ1 protein might thus provide new therapeutic opportunities in MS.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
CHU Lille
Université de Lille
Université de Lille
Date de dépôt :
2019-12-09T16:51:07Z
2021-06-16T07:47:18Z
2021-06-16T07:47:18Z