Abstract
Experimental autoimmune encephalomyelitis (EAE) is a T helper 1 (Th1) cell mediated demyelinating disease and the principal animal model for multiple sclerosis. Spinal cords from SJL mice primed with proteolipid protein peptide 139-151 (pPLP) expressed the chemokines RANTES, MCP-1, MIP-2, KC, MIP-1alpha, MIP-1beta, Mig, and fractalkine. We also identified IP-10 in these samples and described a sequence polymorphism in this transcript. Chemokine expression was specific for tissues of the central nervous system. MCP-1, IP-10, and MIP-2 RNA expression significantly correlated with clinical score. Chemokine receptor expression generally correlated with ligand expression. pPLP-primed mice expressed the Th1-associated markers CCR5 and CXCR3 on mononuclear cells. In addition, cells expressing CCR1, CCR2, CCR3, CCR4, CCR8, and CXCR2 were detected. Here we demonstrate that altered peptide ligand (APL)-induced protection from EAE was accompanied by modulation of chemokine and chemokine receptor expression. Spinal cord tissue sections from APL-protected mice showed greatly reduced levels of all chemokines and of CCR1, CCR5, CCR8, CXCR2 and CXCR3. The Th2-associated chemokine receptors CCR3 and CCR4 were found in protected mice, supporting the hypothesis that Th1 but not Th2 cells are down-regulated by APL treatment. This report concludes that chemokines and chemokine receptors can be useful tools to follow modulation of autoimmune disease.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Chemokine CCL2 / genetics
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Chemokine CCL2 / immunology
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Chemokine CCL3
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Chemokine CCL4
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Chemokine CCL5 / genetics
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Chemokine CCL5 / immunology
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Chemokine CX3CL1
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Chemokine CXCL2
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Chemokine CXCL9
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Chemokines / genetics*
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Chemokines / immunology*
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Chemokines, CX3C*
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Chemokines, CXC / genetics
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Chemokines, CXC / immunology
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DNA, Antisense
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Female
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Gene Expression / drug effects
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Gene Expression / immunology
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Intercellular Signaling Peptides and Proteins*
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Ligands
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Macrophage Inflammatory Proteins / genetics
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Macrophage Inflammatory Proteins / immunology
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Membrane Proteins / genetics
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Membrane Proteins / immunology
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Mice
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Mice, Inbred Strains
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Myelin Proteolipid Protein / immunology
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Myelin Proteolipid Protein / pharmacology*
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Peptide Fragments / immunology
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Peptide Fragments / pharmacology
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Polymorphism, Genetic
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Receptors, CCR1
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Receptors, CCR5 / genetics
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Receptors, CCR5 / immunology
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Receptors, CCR8
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Receptors, CXCR3
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Receptors, Chemokine / genetics*
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Receptors, Chemokine / immunology*
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Receptors, Interleukin-8B / genetics
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Receptors, Interleukin-8B / immunology
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Th1 Cells / chemistry
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Th1 Cells / immunology
Substances
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CCR1 protein, human
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CCR8 protein, human
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CX3CL1 protein, human
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CXCL9 protein, human
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CXCR3 protein, human
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Ccr1 protein, mouse
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Chemokine CCL2
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Chemokine CCL3
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Chemokine CCL4
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Chemokine CCL5
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Chemokine CX3CL1
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Chemokine CXCL2
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Chemokine CXCL9
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Chemokines
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Chemokines, CX3C
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Chemokines, CXC
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Cx3cl1 protein, mouse
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Cxcl2 protein, mouse
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Cxcr3 protein, mouse
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DNA, Antisense
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Intercellular Signaling Peptides and Proteins
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Ligands
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Macrophage Inflammatory Proteins
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Membrane Proteins
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Myelin Proteolipid Protein
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Peptide Fragments
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Receptors, CCR1
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Receptors, CCR5
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Receptors, CCR8
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Receptors, CXCR3
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Receptors, Chemokine
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Receptors, Interleukin-8B