Effects of Imatinib Mesylate in Mouse Models of Multiple Sclerosis and In vitro Determinants
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 k...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Tehran University of Medical Sciences
2014-06-01
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| Series: | Iranian Journal of Allergy, Asthma and Immunology |
| Subjects: | |
| Online Access: | https://ijaai.tums.ac.ir/index.php/ijaai/article/view/456 |
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| author | Gholamreza Azizi Mohsen Reza Haidari Mohammadreza Khorramizadeh Fatemeh Naddafi Reza Sadria Mohammad Hassan Javanbakht Reza Sedaghat Farzaneh Tofighi Zavareh Abbas Mirshafiey |
| author_facet | Gholamreza Azizi Mohsen Reza Haidari Mohammadreza Khorramizadeh Fatemeh Naddafi Reza Sadria Mohammad Hassan Javanbakht Reza Sedaghat Farzaneh Tofighi Zavareh Abbas Mirshafiey |
| author_sort | Gholamreza Azizi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T02:53:57Z |
| format | Article |
| id | doaj.art-8a04556cb3a849d4b75ac40cfe14d293 |
| institution | Directory Open Access Journal |
| issn | 1735-1502 1735-5249 |
| language | English |
| last_indexed | 2024-12-20T02:53:57Z |
| publishDate | 2014-06-01 |
| publisher | Tehran University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Allergy, Asthma and Immunology |
| spelling | doaj.art-8a04556cb3a849d4b75ac40cfe14d2932022-12-21T19:55:57ZengTehran University of Medical SciencesIranian Journal of Allergy, Asthma and Immunology1735-15021735-52492014-06-01133421Effects of Imatinib Mesylate in Mouse Models of Multiple Sclerosis and In vitro DeterminantsGholamreza Azizi0Mohsen Reza Haidari1Mohammadreza Khorramizadeh2Fatemeh Naddafi3Reza Sadria4Mohammad Hassan Javanbakht5Reza Sedaghat6Farzaneh Tofighi Zavareh7Abbas Mirshafiey8Imam Hassan Mojtaba Hospital, Alborz University of Medical Sciences, Karaj, Iran.Department of Neurology, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran.Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.Department of Anatomy and Pathology, Faculty of Medicine, Shahed University, Tehran, Iran.Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.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.https://ijaai.tums.ac.ir/index.php/ijaai/article/view/456Experimental autoimmune encephalomyelitisImatinib mesylateMatrix metalloproteinase-2Multiple Sclerosis |
| spellingShingle | Gholamreza Azizi Mohsen Reza Haidari Mohammadreza Khorramizadeh Fatemeh Naddafi Reza Sadria Mohammad Hassan Javanbakht Reza Sedaghat Farzaneh Tofighi Zavareh Abbas Mirshafiey Effects of Imatinib Mesylate in Mouse Models of Multiple Sclerosis and In vitro Determinants Iranian Journal of Allergy, Asthma and Immunology Experimental autoimmune encephalomyelitis Imatinib mesylate Matrix metalloproteinase-2 Multiple Sclerosis |
| title | Effects of Imatinib Mesylate in Mouse Models of Multiple Sclerosis and In vitro Determinants |
| title_full | Effects of Imatinib Mesylate in Mouse Models of Multiple Sclerosis and In vitro Determinants |
| title_fullStr | Effects of Imatinib Mesylate in Mouse Models of Multiple Sclerosis and In vitro Determinants |
| title_full_unstemmed | Effects of Imatinib Mesylate in Mouse Models of Multiple Sclerosis and In vitro Determinants |
| title_short | Effects of Imatinib Mesylate in Mouse Models of Multiple Sclerosis and In vitro Determinants |
| title_sort | effects of imatinib mesylate in mouse models of multiple sclerosis and in vitro determinants |
| topic | Experimental autoimmune encephalomyelitis Imatinib mesylate Matrix metalloproteinase-2 Multiple Sclerosis |
| url | https://ijaai.tums.ac.ir/index.php/ijaai/article/view/456 |
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