(2015) Prophylactic Effect of BIO-1211 Small-Molecule Antagonist of VLA-4 in the EAE Mouse Model of Multiple Sclerosis. Immunological Investigations. pp. 694-712. ISSN 0882-0139
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Abstract
Background and Purpose: Some functional limitations and economic burden of therapeutic antibodies indicated that introducing of alternative therapeutic compounds with same or different mechanism of action could be worthwhile. In this regard small-molecule antagonists can have a wide range of impacts, so in this research, we examine the prophylactic effects of BIO-1211 Very Late Antigen-4 (VLA4) blocker, in experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis in comparison with commercial available medicine, Natalizumab (NTZ).Methods: EAE was induced by subcutaneous immunization of myelin oligodendrocyte glycoprotein (MOG35-55) in 8-week-old C57BL/6 mice. During EAE induction, mice were separated to distinct groups and provided either BIO-1211 (5 and 10mg/kg) or NTZ (5mg/kg) and co-administration of these two compounds. After 21 days, neuro-inflammatory responses were analyzed using qRT-PCR, western blot, and ELISA methods. Pervade of immune cells to brain was examined by Evans blue staining and immunohistochemistry (IHC) analysis of specific markers of microglia/monocytes (CD11b) and leukocytes (CD45).Results: Targeted disruption of VLA4/VCAM1 interactions, by BIO-1211 agonist in mice, results in reduced cytokines expression, leukocyte trafficking, and inhibition of inflammatory responses in EAE (p<0.01) in a dose-independent manner (data not shown). Mice treated with both BIO-1211 and NTZ exhibited a considerable depletion in the EAE clinical score, which correlated with decreased expression of TNF-, IL-17, IFN- and pervade of CD11b(+) and CD45(+) cells into the cerebral cortex.Conclusion: Our results indicated that BIO12-11 compound would be an useful tool to further understand the biological roles of VLA4/VCAM1 interactions, and could also be considered as EAE-suppressing agent.
Item Type: | Article |
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Keywords: | bio-1211 eae multiple sclerosis neuro-inflammation vla4 experimental autoimmune encephalomyelitis nitric-oxide synthase cortical demyelination animal-model in-vivo alpha-4-beta-1 integrin different subtypes iranian patients c57bl/6 mice spinal-cord |
Divisions: | |
Page Range: | pp. 694-712 |
Journal or Publication Title: | Immunological Investigations |
Volume: | 44 |
Number: | 7 |
Identification Number: | 10.3109/08820139.2015.1085391 |
ISSN: | 0882-0139 |
Depositing User: | مهندس مهدی شریفی |
URI: | http://eprints.zbmu.ac.ir/id/eprint/2663 |
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