Therapeutic effects of dasatinib in mouse model of multiple sclerosis

• Published in: Immunopharmacology and immunotoxicology 2015-06, Vol.37 (3), p.287-294
• Main Authors: Azizi, Gholamreza, Goudarzvand, Mahdi, Afraei, Sanaz, Sedaghat, Reza, Mirshafiey, Abbas
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; Dasatinib; Dasatinib - pharmacology; Encephalomyelitis, Autoimmune, Experimental - chemically induced; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; experimental autoimmune encephalomyelitis; Female; Matrix Metalloproteinase 2 - immunology; matrix metalloproteinase-2; Mice; multiple sclerosis; Multiple Sclerosis - chemically induced; Multiple Sclerosis - drug therapy; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Myelin-Oligodendrocyte Glycoprotein - toxicity; nitric oxide; Nitric Oxide - immunology; Peptide Fragments - toxicity; Tumor Necrosis Factor-alpha - immunology
• ISSN: 0892-3973; 1532-2513
• DOI: 10.3109/08923973.2015.1028074

Abstract Background: Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. Dasatinib (Sprycel) is a selective protein tyrosine kinase inhibitor with immunomodulatory properties that abrogates multiple signal transduction pathways in immune cells. In the present research, our aim was to test the therapeutic efficacy of dasatinib in experimental model of MS. Methods: We performed EAE induction in female C57BL/6 mice by myelin oligodendrocyte glycoprotein35-55 (MOG35-55) in Complete Freund's Adjuvant (CFA) emulsion, and used dasatinib for the treatment of EAE. During the course of study, clinical evaluation was assessed, and on day 21 post-immunization blood samples were taken from the heart of mice for tumor necrosis factor-alpha (TNF-α), nitric oxide (NO) and antioxidants capacity evaluation. The mice were sacrificed and brains and cerebellums of mice were removed for histological analysis. Also for in vitro analysis, we used C6 astrocytoma cell line to evaluate the inhibitory effects of dasatinib in cell proliferation and matrix metalloproteinase-2 (MMP-2) activity. Results: Our findings demonstrated that dasatinib had beneficial effects on EAE by lower incidence, attenuation in the severity and a delay in the onset of disease. The serum level of NO and TNF-α in dasatinib treated mice was significantly lower than control mice. In vitro, dasatinib inhibited cell proliferation and MMP-2 activity. Conclusion: Dasatinib with its potential therapeutic effects and immunomodulatory properties may be recommended, after additional necessary tests and trials, for the treatment of MS.