Abstract
Idiopathic inflammatory myopathy is a chronic inflammatory muscle disease characterized by mononuclear cell infiltration in the skeletal muscle. The infiltrated inflammatory cells express various cytokines and cytotoxic molecules. Chemokines are thought to contribute to the inflammatory cell migration into the muscle. We induced experimental autoimmune myositis (EAM) in SJL/J mice by immunization with rabbit myosin and CFA. In the affected muscles of EAM mice, CX3CL1 (fractalkine) was expressed on the infiltrated mononuclear cells and endothelial cells, and its corresponding receptor, CX3CR1, was expressed on the infiltrated CD4 and CD8 T cells and macrophages. Treatment of EAM mice with anti-CX3CL1 mAb significantly reduced the histopathological myositis score, the number of necrotic muscle fibers, and infiltration of CD4 and CD8 T cells and macrophages. Furthermore, treatment with anti-CX3CL1 mAb down-regulated the mRNA expression of TNF-alpha, IFN-gamma, and perforin in the muscles. Our results suggest that CX3CL1-CX3CR1 interaction plays an important role in inflammatory cell migration into the muscle tissue of EAM mice. The results also point to the potential therapeutic usefulness of CX3CL1 inhibition and/or blockade of CX3CL1-CX3CR1 interaction in idiopathic inflammatory myopathy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / pharmacology
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Base Sequence
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / pathology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / pathology
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CX3C Chemokine Receptor 1
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Chemokine CX3CL1
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Chemokines, CX3C / antagonists & inhibitors*
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Chemokines, CX3C / metabolism
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Down-Regulation
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Interferon-gamma / genetics
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Macrophages / immunology
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Macrophages / pathology
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Male
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Membrane Proteins / antagonists & inhibitors*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Muscle, Skeletal / immunology
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Muscle, Skeletal / metabolism
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Muscle, Skeletal / pathology
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Nervous System Autoimmune Disease, Experimental / genetics
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Nervous System Autoimmune Disease, Experimental / immunology
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Nervous System Autoimmune Disease, Experimental / pathology
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Nervous System Autoimmune Disease, Experimental / therapy*
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Pore Forming Cytotoxic Proteins
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Chemokine / metabolism
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Tumor Necrosis Factor-alpha / genetics
Substances
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Antibodies, Monoclonal
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CX3C Chemokine Receptor 1
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Chemokine CX3CL1
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Chemokines, CX3C
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Cx3cl1 protein, mouse
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Cx3cr1 protein, mouse
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Membrane Proteins
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Pore Forming Cytotoxic Proteins
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RNA, Messenger
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Receptors, Chemokine
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Tumor Necrosis Factor-alpha
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perforin, mouse
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Interferon-gamma