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Anti-Inflammatory Effect of KW-2449 on Autoimmune Encephalomyelitis: An Experimental Study on Mice

Author(s):

Hasan Namdar Ahmadabad, Allireza Abbaspour, Yaser Panahi, Saeed Tahmasebi, Nikoo Hossein‐khannazer, Sanaz Afraei, Hosein Miladi, Mahdi Goudarzvand, Ali N. Kamali, Yasser Bagheri, Reza Yazdani, Maria Maddalena Di Fiore and Gholamreza Azizi*   Pages 1 - 8 ( 8 )

Abstract:


Background: The KW-2449 is a novel multikinase inhibitor that inhibits FLT3, ABL, ABL-T315I, and Aurora A. FLT3 and Aurora A kinases play an important role in the pathogenesis of multiple sclerosis (MS). KW-2449 could modulate immune cells but the immunomodulatory effects of KW-2449 on experimental autoimmune encephalomyelitis (EAE) have not been investigated yet. The aim of the present study is to investigate the effects of KW-2449 on EAE mouse model.

Methods: In this study, C57BL/6 EAE mice were orally treated with (10 mg/kg/day) KW-2449 solution and compared with both EAE and control mice. Following the treatment, histological analyses were performed on brain and cerebellums to evaluate the pathological score. The gene expression levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and chemokine (C-C motif) ligand 2 (CCL2) were measured using qRT-PCR. The serum levels of TNF-α, IL-6, CCL-2 and MMP-2 were determined by using quantitative enzyme-linked immunosorbent assay (ELISA).

Results: The results indicated that the clinical score, the infiltration of inflammatory cells and the demyelination in EAE mice treated with KW-2449 decreased significantly compared to control groups. KW-2449 also decreased TNF-α, IL-6, CCL-2 inflammatory cytokines and MMP-2 in both brain mRNA expressions and serum levels of EAE mice.

Conclusion: The KW-2449, aging as a multi-kinase inhibitor, modulates the inflammatory responses of cytokine cascades either in brain or in plasma and reduces EAE pathogenesis manifestation.

Keywords:

Experimental autoimmune encephalomyelitis, KW-2449, Multiple sclerosis, TNF-α, IL-6, CCL-2, MMP-2

Affiliation:

Department of Pathobiology and Laboratory Sciences, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Department of Pathobiology and Laboratory Sciences, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Department of Pathobiology and Laboratory Sciences, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Research Center for Applied Plant Sciences, Arak Branch, Islamic Azad University, Arak, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Department of Cell and Molecular Biology, University of Tehran, Tehran, Department of Pathology, Imam Khomeini Hospital Affiliated to Social Security Organization, Arak, Department of Physiology and Pharmacology, School of medicine, Alborz University of Medical Sciences, Karaj, CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Clinical Research Development Unit (CRDU), 5 azar Hospital, Golestan University of Medical Sciences, Gorgan, Research Centre for Immunodeficiencies, Children's Medical Centre, Tehran University of Medical Sciences, Tehran, Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Via Vivaldi 43, 81100 Caserta, Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj



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