Prophylactic Effect of BIO-1211 Small-Molecule Antagonist of VLA-4 in the EAE Mouse Model of Multiple Sclerosis |
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Authors: | Nourollah Ramroodi Masood Khani Zohre Ganjali Mohammad Reza Javan Roghayeh Khalseh |
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Institution: | 1. Department of Neurology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran,;2. Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran,;3. Department of Biology, Faculty of Sciences, University of Zabol, Zabol, Iran,;4. Department of Immunology, Faculty of Medicine, Zabol University of Medical Sciences, Zabol, Iran,;5. Department of Chemical Engineering, Babol Noushirvani University of Technology, Babol, Iran, |
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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 10?mg/kg) or NTZ (5?mg/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-α, IL-17, IFN-γ 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. |
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Keywords: | BIO-1211 EAE multiple sclerosis neuro-inflammation VLA4 |
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