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 methods: Peripheral 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. Results: CXCL10- 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. Conclusions: MP 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. (C) 2016 Polish Neurological Society. Published by Elsevier Sp. z o.o. All rights reserved.
机构:
QIMR Berghofer Med Res Inst, Cellular Immunol Lab, Brisbane, Qld 4029, Australia
Univ Queensland, Sch Med, Brisbane, Qld 4029, Australia
Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia
QIMR Berghofer Med Res Inst, Brisbane, Qld, AustraliaQIMR Berghofer Med Res Inst, Cellular Immunol Lab, Brisbane, Qld 4029, Australia
Pender, Michael P.
Csurhes, Peter A.
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Univ Queensland, Sch Med, Brisbane, Qld 4029, Australia
Univ Queensland, Clin Res Ctr, Brisbane, Qld 4029, AustraliaQIMR Berghofer Med Res Inst, Cellular Immunol Lab, Brisbane, Qld 4029, Australia
Csurhes, Peter A.
Pfluger, Casey M. M.
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Univ Queensland, Sch Med, Brisbane, Qld 4029, Australia
Univ Queensland, Clin Res Ctr, Brisbane, Qld 4029, AustraliaQIMR Berghofer Med Res Inst, Cellular Immunol Lab, Brisbane, Qld 4029, Australia
Pfluger, Casey M. M.
Burrows, Scott R.
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Univ Queensland, Sch Med, Brisbane, Qld 4029, Australia
QIMR Berghofer Med Res Inst, Brisbane, Qld, AustraliaQIMR Berghofer Med Res Inst, Cellular Immunol Lab, Brisbane, Qld 4029, Australia
机构:
Univ Tampere, Sch Med, Neuroimmunol Unit, FIN-33014 Tampere, Finland
Tampere Univ Hosp, Dept Neurol, Tampere, FinlandUniv Tampere, Sch Med, Neuroimmunol Unit, FIN-33014 Tampere, Finland
Elovaara, Irina
Kuusisto, Hanna
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Univ Tampere, Sch Med, Neuroimmunol Unit, FIN-33014 Tampere, Finland
Tampere Univ Hosp, Dept Neurol, Tampere, Finland
Kanta Hame Cent Hosp, Dept Neurol, Hameenlinna, FinlandUniv Tampere, Sch Med, Neuroimmunol Unit, FIN-33014 Tampere, Finland
Kuusisto, Hanna
Wu, Xingchen
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Univ Tampere, Sch Med, Neuroimmunol Unit, FIN-33014 Tampere, Finland
Tampere Univ Hosp, Dept Diagnost Imaging, Tampere, FinlandUniv Tampere, Sch Med, Neuroimmunol Unit, FIN-33014 Tampere, Finland
Wu, Xingchen
Rinta, Sanna
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Univ Tampere, Sch Med, Neuroimmunol Unit, FIN-33014 Tampere, FinlandUniv Tampere, Sch Med, Neuroimmunol Unit, FIN-33014 Tampere, Finland
Rinta, Sanna
Dastidar, Prasun
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Tampere Univ Hosp, Dept Diagnost Imaging, Tampere, FinlandUniv Tampere, Sch Med, Neuroimmunol Unit, FIN-33014 Tampere, Finland
Dastidar, Prasun
Reipert, Birgit
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Baxter BioSci, Vienna, AustriaUniv Tampere, Sch Med, Neuroimmunol Unit, FIN-33014 Tampere, Finland