| Anti-IL-6-receptor antibody promotes repair of spinal cord injury by inducing microglia-dominant inflammation. | |
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MedLine Citation:
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PMID: 20478301 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We previously reported the beneficial effect of administering an anti-mouse IL-6 receptor antibody (MR16-1) immediately after spinal cord injury (SCI). The purpose of our present study was to clarify the mechanism underlying how MR16-1 improves motor function after SCI. Quantitative analyses of inflammatory cells using flow cytometry, and immunohistochemistry with bone marrow-chimeric mice generated by transplanting genetically marked purified hematopoietic stem cells, revealed that MR16-1 dramatically switched the central player in the post-traumatic inflammation, from hematogenous macrophages to resident microglia. This change was accompanied by alterations in the expression of relevant cytokines within the injured spinal cord; the expression of recruiting chemokines including CCL2, CCL5, and CXCL10 was decreased, while that of Granulocyte/Macrophage-Colony Stimulating Factor (GM-CSF), a known mitogen for microglia, was increased. We also showed that the resident microglia expressed higher levels of phagocytic markers than the hematogenous macrophages. Consistent with these findings, we observed significantly decreased tissue damage and reduced levels of myelin debris and Nogo-A, the axonal growth inhibitor, by MR16-1 treatment. Moreover, we observed increased axonal regeneration and/or sprouting in the MR16-1-treated mice. Our findings indicate that the functional improvement elicited by MR16-1 involves microglial functions, and provide new insights into the role of IL-6 signaling in the pathology of SCI. |
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Authors:
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Masahiko Mukaino; Masaya Nakamura; Osamu Yamada; Seiji Okada; Satoru Morikawa; Francois Renault-Mihara; Akio Iwanami; Takeshi Ikegami; Yoshiyuki Ohsugi; Osahiko Tsuji; Hiroyuki Katoh; Yumi Matsuzaki; Yoshiaki Toyama; Meigen Liu; Hideyuki Okano |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-16 |
Journal Detail:
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Title: Experimental neurology Volume: 224 ISSN: 1090-2430 ISO Abbreviation: Exp. Neurol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-19 Completed Date: 2010-07-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370712 Medline TA: Exp Neurol Country: United States |
Other Details:
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Languages: eng Pagination: 403-14 Citation Subset: IM |
Copyright Information:
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(c) 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Rehabilitation Medicine, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / therapeutic use* Chemokines / biosynthesis Chimera Female Granulocyte-Macrophage Colony-Stimulating Factor / metabolism Hematopoietic Stem Cell Transplantation Inflammation / immunology Macrophages / drug effects, immunology Mice Mice, Transgenic Microglia / drug effects*, immunology Phagocytosis Rats Receptors, Interleukin-6 / immunology* Spinal Cord / drug effects, immunology, pathology Spinal Cord Injuries / drug therapy*, immunology, pathology |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Chemokines; 0/Receptors, Interleukin-6; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor |
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