The selective M-CSF receptor tyrosine kinase inhibitor Ki20227 suppresses experimental autoimmune encephalomyelitis
| Autor: | Hiroaki Ohno, Hideko Murooka, Yumiko Ohzeki, Yasunori Uemura, Hiromi Takanashi, Kazuo Kubo, Isao Serizawa |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Encephalomyelitis Autoimmune Experimental Time Factors medicine.drug_class T-Lymphocytes T cell Immunology Biology Lymphocyte Activation Tyrosine-kinase inhibitor Myelin oligodendrocyte glycoprotein Mice Myelin Immune system Antigens CD medicine Animals Immunology and Allergy Receptor Protein Kinase Inhibitors Cell Proliferation Dose-Response Relationship Drug Phenylurea Compounds Experimental autoimmune encephalomyelitis Mononuclear phagocyte system Flow Cytometry medicine.disease Mice Inbred C57BL Myelin-Associated Glycoprotein Thiazoles medicine.anatomical_structure Spinal Cord Neurology biology.protein Cytokines Myelin-Oligodendrocyte Glycoprotein Neurology (clinical) Myelin Proteins |
| Zdroj: | Journal of Neuroimmunology. 195:73-80 |
| ISSN: | 0165-5728 |
| DOI: | 10.1016/j.jneuroim.2008.01.015 |
| Popis: | Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), can be induced by the immunization of mice with myelin antigens in the form of myelin oligodendrocyte glycoprotein (MOG). Macrophage colony-stimulating factor (M-CSF) is required for the development of individual mononuclear phagocyte populations and is involved in the immune response. We previously reported that Ki20227 (N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methoxyphenyl}-N'-[1-(1,3-thiazole-2-yl)ethyl]urea) is a highly selective M-CSF receptor (c-fms) tyrosine kinase inhibitor. In our current study, we investigated whether Ki20227 has suppressive effects upon EAE and indeed found that this drug significantly reduced the severity of this disease both preventively and therapeutically. Notably also, Ki20227 treatments inhibited the turn-over/expansion of myeloid cells provoked by the immunization and subsequent MOG-specific T cell responses in our EAE animal model. These findings suggest that M-CSF plays a pivotal role in the development of EAE and that Ki20227 and its derivatives may be candidate drugs for the treatment of human MS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect