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Prophylactic Effect of Bio-1211 Small-Molecule Antagonist of Vla-4 in the Eae Mouse Model of Multiple Sclerosis Publisher Pubmed



Ramroodi N1 ; Khani M2 ; Ganjali Z3 ; Javan MR4 ; Sanadgol N3, 5 ; Khalseh R6 ; Ravan H7 ; Sanadgol E8 ; Abdollahi M5
Authors
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Authors Affiliations
  1. 1. Department of Neurology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
  2. 2. Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Department of Biology, Faculty of Sciences, University of Zabol, Zabol, Iran
  4. 4. Department of Immunology, Faculty of Medicine, Zabol University of Medical Sciences, Zabol, Iran
  5. 5. Department of Pharmacy and Pharmaceutical Science Research Center, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Chemical Engineering, Babol Noushirvani University of Technology, Babol, Iran
  7. 7. Department of Biology, Faculty of Science, Shahid Bahonar University of Kerman, Kerman, Iran
  8. 8. Department of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Source: Immunological Investigations Published:2015


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. © 2015 © 2015 Taylor & Francis Group, LLC.
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