title: Effects of imatinib mesylate in mouse models of multiple sclerosis and in vitro determinants.
abstract: Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis (MS), This autoimmune disease is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. Imatinib mesylate 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 imatinib in experimental model of MS. We performed EAE induction in 23 female C57 mice by myelin oligodendrocyte glycoprotein-35-55 (MOG35-55) in Complete Freund's Adjuvant (CFA) emulsion and used imatinib for treatment of EAE. The clinical evaluation and histopathology were assessed. Also for in vitro analysis, we used U-87 MG, C6 and WEHI-164 cell lines to evaluate the inhibitory effects of imatinib in cell proliferation, as well as pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and matrix metalloproteinase (MMP) secretion. Our findings demonstrated that this drug had beneficial effects on EAE by attenuation in the severity and a delay in the onset of disease. In vitro, imatinib inhibited cell proliferation, MMP-2 expression and activity and also attenuated the production of proinflammatory cytokines. Imatinib with its potential therapeutic effects and immunomodulatory properties may be considered, after additional necessary tests and trials, for treatment of MS.
authors.affiliation: Imam Hassan Mojtaba Hospital, Alborz University of Medical Sciences, Karaj, Iran. Azizi_g@razi.tums.ac.ir.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Azizi
authors.affiliation: Department of Neurology, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran. abba_mirshafiey@yahoo.com.
authors.forename: Mohsen Reza
authors.initials: MR
authors.lastname: Haidari
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Khorramizadeh@yahoo.com.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Khorramizadeh
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Fatemeh.Naddafi@yahoo.com.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Naddafi
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. reza.sadria@gmail.com.
authors.forename: Reza
authors.initials: R
authors.lastname: Sadria
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. mhjavan2001@gmail.com.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Javanbakht
authors.affiliation: Department of Anatomy and Pathology, Faculty of Medicine, Shahed University, Tehran, Iran. azizi1357g@gmail.com.
authors.forename: Reza
authors.initials: R
authors.lastname: Sedaghat
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. mirshafiey@tums.ac.ir.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Tofighi Zavareh
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. mirshafiey@tums.ac.ir.
authors.forename: Abbas
authors.initials: A
authors.lastname: Mirshafiey
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005260:Female; D000068877:Imatinib Mesylate; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D016207:Cytokines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D020778:Matrix Metalloproteinase 2