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The impact of multiple sclerosis relapse treatment on migration of effector T cells – Preliminary study
Affiliations- Department of Propedeutics of Neurology, Medical University of Lodz, Lodz, Poland
- Department of Neurology and Stroke, Medical University of Lodz, Lodz, Poland
- Department of Laboratory Diagnostics, Medical University of Lodz, Lodz, Poland
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Abstract
Migration of inflammatory cells from the blood to the central nervous system (CNS) is crucial for development of multiple sclerosis (MS). Inhibition of this process would allow to control disease activity. The first step confirming this approach would be the analysis of the impact of effective MS relapse therapy on migration of effector T cells. The aim of the study was to analyze the influence of methylprednisolone (MP) on the migratory activity of effector CD4+ T cells from MS patients. Moreover, to study the potential mechanism of this process we studied expression of chemokine receptors on migrating cells.
Material and methodsPeripheral blood samples were obtained from relapsing-remitting MS (RR-MS) patients during relapse (n=23) and from control group (n=23). After isolation CD4+ T cells were incubated with various concentrations of MP. Then they were stimulated in chemotaxis assay with chemokines CCL3 or CXCL10 or were used to CCR1 and CXCR3 expression analysis.
ResultsCXCL10- and CCL3-stimulated migration of CD4+ T cells was significantly increased in MS. MP was able to reduce in vitro migration of effector T cells induced by CXCL10, but not by CCL3. Inhibition by MP was dose-dependent. Expression of analyzed chemokine receptors was unaltered after MP incubation.
ConclusionsMP reduced CD4+ T cells migration induced by CXCL10 without affecting CXCR3 expression. These observations demonstrate one of the potential mechanisms of MP action in MS, distinct from inducing cell apoptosis, and suggests the new targets for development of more effective MS treatments.
Abstract
Migration of inflammatory cells from the blood to the central nervous system (CNS) is crucial for development of multiple sclerosis (MS). Inhibition of this process would allow to control disease activity. The first step confirming this approach would be the analysis of the impact of effective MS relapse therapy on migration of effector T cells. The aim of the study was to analyze the influence of methylprednisolone (MP) on the migratory activity of effector CD4+ T cells from MS patients. Moreover, to study the potential mechanism of this process we studied expression of chemokine receptors on migrating cells.
Material and methodsPeripheral blood samples were obtained from relapsing-remitting MS (RR-MS) patients during relapse (n=23) and from control group (n=23). After isolation CD4+ T cells were incubated with various concentrations of MP. Then they were stimulated in chemotaxis assay with chemokines CCL3 or CXCL10 or were used to CCR1 and CXCR3 expression analysis.
ResultsCXCL10- and CCL3-stimulated migration of CD4+ T cells was significantly increased in MS. MP was able to reduce in vitro migration of effector T cells induced by CXCL10, but not by CCL3. Inhibition by MP was dose-dependent. Expression of analyzed chemokine receptors was unaltered after MP incubation.
ConclusionsMP reduced CD4+ T cells migration induced by CXCL10 without affecting CXCR3 expression. These observations demonstrate one of the potential mechanisms of MP action in MS, distinct from inducing cell apoptosis, and suggests the new targets for development of more effective MS treatments.
Keywords
Methylprednisolone, Multiple sclerosis, Migration, Chemokines, Chemokine receptors
About this articleTitle
The impact of multiple sclerosis relapse treatment on migration of effector T cells – Preliminary study
Journal
Neurologia i Neurochirurgia Polska
Issue
Pages
155-162
Page views
341
Article views/downloads
594
DOI
10.1016/j.pjnns.2016.02.003
Bibliographic record
Neurol Neurochir Pol 2016;50(3):155-162.
Keywords
Methylprednisolone
Multiple sclerosis
Migration
Chemokines
Chemokine receptors
Authors
Izabela Jatczak-Pawlik
Dominika Książek-Winiarek
Dagmara Wojkowska
Krzysztof Jóźwiak
Karol Jastrzębski
Mirosława Pietruczuk
Andrzej Głąbiński
