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Suppression of autoimmune encephalomyelitis by a neurokinin-1 receptor antagonist — A putative role for substance P in CNS inflammation
Substance P (SP) is an excitatory neurotransmitter in the central and peripheral nervous system. Most of its physiological functions are mediated through binding to the neurokinin-1 receptor (NK-1R). Recently, proinflammatory properties of SP have been described. In this study we utilized T cell tra...
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Published in: | Journal of neuroimmunology 2006-10, Vol.179 (1), p.1-8 |
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description | Substance P (SP) is an excitatory neurotransmitter in the central and peripheral nervous system. Most of its physiological functions are mediated through binding to the neurokinin-1 receptor (NK-1R). Recently, proinflammatory properties of SP have been described. In this study we utilized T cell transfer experimental autoimmune encephalomyelitis (EAE) to investigate the role of SP in CNS autoimmune disease. Treatment with the NK-1R antagonist CP-96,345 dramatically reduced clinical and histological signs of EAE if administered before disease onset. The protective effect of CP96,345 treatment was related to a reduced expression of the adhesion molecules ICAM-1 and VCAM-1 on CNS endothelia. The cellular composition or activation status of splenocytes was not affected by CP-96,345 administration, while the secretion of proinflammatory Th1 cytokines was reduced in treated animals. Th2 cytokines remained largely unaffected by NK-1 receptor antagonist treatment. In summary, our findings suggest that the protective effect of CP96,345 treatment is mediated by stabilization of the blood–brain barrier and suppression of Th1 immunity. |
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Most of its physiological functions are mediated through binding to the neurokinin-1 receptor (NK-1R). Recently, proinflammatory properties of SP have been described. In this study we utilized T cell transfer experimental autoimmune encephalomyelitis (EAE) to investigate the role of SP in CNS autoimmune disease. Treatment with the NK-1R antagonist CP-96,345 dramatically reduced clinical and histological signs of EAE if administered before disease onset. The protective effect of CP96,345 treatment was related to a reduced expression of the adhesion molecules ICAM-1 and VCAM-1 on CNS endothelia. The cellular composition or activation status of splenocytes was not affected by CP-96,345 administration, while the secretion of proinflammatory Th1 cytokines was reduced in treated animals. Th2 cytokines remained largely unaffected by NK-1 receptor antagonist treatment. 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Most of its physiological functions are mediated through binding to the neurokinin-1 receptor (NK-1R). Recently, proinflammatory properties of SP have been described. In this study we utilized T cell transfer experimental autoimmune encephalomyelitis (EAE) to investigate the role of SP in CNS autoimmune disease. Treatment with the NK-1R antagonist CP-96,345 dramatically reduced clinical and histological signs of EAE if administered before disease onset. The protective effect of CP96,345 treatment was related to a reduced expression of the adhesion molecules ICAM-1 and VCAM-1 on CNS endothelia. The cellular composition or activation status of splenocytes was not affected by CP-96,345 administration, while the secretion of proinflammatory Th1 cytokines was reduced in treated animals. Th2 cytokines remained largely unaffected by NK-1 receptor antagonist treatment. In summary, our findings suggest that the protective effect of CP96,345 treatment is mediated by stabilization of the blood–brain barrier and suppression of Th1 immunity.</description><subject>Adhesion molecules</subject><subject>Adoptive Transfer</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Autoimmune encephalomyelitis</subject><subject>Biphenyl Compounds - pharmacology</subject><subject>Blood-Brain Barrier - drug effects</subject><subject>Central Nervous System - drug effects</subject><subject>Central Nervous System - immunology</subject><subject>Central Nervous System - pathology</subject><subject>Cytokines - drug effects</subject><subject>Cytokines - secretion</subject><subject>Encephalomyelitis, Autoimmune, Experimental - immunology</subject><subject>Encephalomyelitis, Autoimmune, Experimental - pathology</subject><subject>Encephalomyelitis, Autoimmune, Experimental - prevention & control</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>ICAM-1</subject><subject>Immunohistochemistry</subject><subject>Inflammation - immunology</subject><subject>Inflammation - pathology</subject><subject>Inflammation - prevention & control</subject><subject>Intercellular Adhesion Molecule-1 - biosynthesis</subject><subject>Intercellular Adhesion Molecule-1 - drug effects</subject><subject>Mice</subject><subject>Neurokinin-1 Receptor Antagonists</subject><subject>NK-1 receptor</subject><subject>Substance P</subject><subject>Substance P - immunology</subject><subject>T-Lymphocytes - drug effects</subject><subject>Vascular Cell Adhesion Molecule-1 - biosynthesis</subject><subject>Vascular Cell Adhesion Molecule-1 - drug effects</subject><subject>VCAM-1</subject><issn>0165-5728</issn><issn>1872-8421</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNqFkctu1DAUhi1ERYfCK1RescvgS2I7O6oRN6mCSi1ry4lPwENiB9upNDu27HlCnqQOM4hlpSOdzXf-XzofQpeUbCmh4vV-u_ewxOCmLSNEbNdh4gnaUCVZpWpGn6JNAZuqkUydo-cp7QmhDa_bZ-icipbUtGUb9Ot2mecIKbngcRiwWXLJnBYPGHwP8zczhukAo8su4e6ADf5b-9155yuKIxQmh4iNz-Zr8C5l_Ofnb3yF5yWb7O4BxzACHgqSli5lU0LxDXYe7z7dljWMZpoKGPwLdDaYMcHL075AX969vdt9qK4_v_-4u7quet7KXLVk4IPqZM0aITpWC6KAWwmWyt5wMjSqU3UtGmkbS7k1g-iFYFT0nZWGEMMv0Ktj7hzDjwVS1pNLPYyj8RCWpIVqaS04exSkLVe1bHkBxRHsY0gpwqDn6CYTD5oSvdrSe_3Pll5t6XWYKIeXp4alm8D-PzvpKcCbIwDlIfcOok69W71YVz6ftQ3usY4HkJKtHA</recordid><startdate>20061001</startdate><enddate>20061001</enddate><creator>Nessler, Stefan</creator><creator>Stadelmann, Christine</creator><creator>Bittner, Alwina</creator><creator>Schlegel, Kerstin</creator><creator>Gronen, Felix</creator><creator>Brueck, Wolfgang</creator><creator>Hemmer, Bernhard</creator><creator>Sommer, Norbert</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20061001</creationdate><title>Suppression of autoimmune encephalomyelitis by a neurokinin-1 receptor antagonist — A putative role for substance P in CNS inflammation</title><author>Nessler, Stefan ; Stadelmann, Christine ; Bittner, Alwina ; Schlegel, Kerstin ; Gronen, Felix ; Brueck, Wolfgang ; Hemmer, Bernhard ; Sommer, Norbert</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c397t-90f3f8b742566b24608e3d7ed17ca30f58b844657d5d13daf6c66216cbd7a00a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adhesion molecules</topic><topic>Adoptive Transfer</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Autoimmune encephalomyelitis</topic><topic>Biphenyl Compounds - pharmacology</topic><topic>Blood-Brain Barrier - drug effects</topic><topic>Central Nervous System - drug effects</topic><topic>Central Nervous System - immunology</topic><topic>Central Nervous System - pathology</topic><topic>Cytokines - drug effects</topic><topic>Cytokines - secretion</topic><topic>Encephalomyelitis, Autoimmune, Experimental - immunology</topic><topic>Encephalomyelitis, Autoimmune, Experimental - pathology</topic><topic>Encephalomyelitis, Autoimmune, Experimental - prevention & control</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>ICAM-1</topic><topic>Immunohistochemistry</topic><topic>Inflammation - immunology</topic><topic>Inflammation - pathology</topic><topic>Inflammation - prevention & control</topic><topic>Intercellular Adhesion Molecule-1 - biosynthesis</topic><topic>Intercellular Adhesion Molecule-1 - drug effects</topic><topic>Mice</topic><topic>Neurokinin-1 Receptor Antagonists</topic><topic>NK-1 receptor</topic><topic>Substance P</topic><topic>Substance P - immunology</topic><topic>T-Lymphocytes - drug effects</topic><topic>Vascular Cell Adhesion Molecule-1 - biosynthesis</topic><topic>Vascular Cell Adhesion Molecule-1 - drug effects</topic><topic>VCAM-1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nessler, Stefan</creatorcontrib><creatorcontrib>Stadelmann, Christine</creatorcontrib><creatorcontrib>Bittner, Alwina</creatorcontrib><creatorcontrib>Schlegel, Kerstin</creatorcontrib><creatorcontrib>Gronen, Felix</creatorcontrib><creatorcontrib>Brueck, Wolfgang</creatorcontrib><creatorcontrib>Hemmer, Bernhard</creatorcontrib><creatorcontrib>Sommer, Norbert</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neuroimmunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nessler, Stefan</au><au>Stadelmann, Christine</au><au>Bittner, Alwina</au><au>Schlegel, Kerstin</au><au>Gronen, Felix</au><au>Brueck, Wolfgang</au><au>Hemmer, Bernhard</au><au>Sommer, Norbert</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Suppression of autoimmune encephalomyelitis by a neurokinin-1 receptor antagonist — A putative role for substance P in CNS inflammation</atitle><jtitle>Journal of neuroimmunology</jtitle><addtitle>J Neuroimmunol</addtitle><date>2006-10-01</date><risdate>2006</risdate><volume>179</volume><issue>1</issue><spage>1</spage><epage>8</epage><pages>1-8</pages><issn>0165-5728</issn><eissn>1872-8421</eissn><abstract>Substance P (SP) is an excitatory neurotransmitter in the central and peripheral nervous system. Most of its physiological functions are mediated through binding to the neurokinin-1 receptor (NK-1R). Recently, proinflammatory properties of SP have been described. In this study we utilized T cell transfer experimental autoimmune encephalomyelitis (EAE) to investigate the role of SP in CNS autoimmune disease. Treatment with the NK-1R antagonist CP-96,345 dramatically reduced clinical and histological signs of EAE if administered before disease onset. The protective effect of CP96,345 treatment was related to a reduced expression of the adhesion molecules ICAM-1 and VCAM-1 on CNS endothelia. The cellular composition or activation status of splenocytes was not affected by CP-96,345 administration, while the secretion of proinflammatory Th1 cytokines was reduced in treated animals. Th2 cytokines remained largely unaffected by NK-1 receptor antagonist treatment. In summary, our findings suggest that the protective effect of CP96,345 treatment is mediated by stabilization of the blood–brain barrier and suppression of Th1 immunity.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>16904192</pmid><doi>10.1016/j.jneuroim.2006.06.026</doi><tpages>8</tpages></addata></record> |
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subjects | Adhesion molecules Adoptive Transfer Animals Anti-Inflammatory Agents, Non-Steroidal - pharmacology Autoimmune encephalomyelitis Biphenyl Compounds - pharmacology Blood-Brain Barrier - drug effects Central Nervous System - drug effects Central Nervous System - immunology Central Nervous System - pathology Cytokines - drug effects Cytokines - secretion Encephalomyelitis, Autoimmune, Experimental - immunology Encephalomyelitis, Autoimmune, Experimental - pathology Encephalomyelitis, Autoimmune, Experimental - prevention & control Endothelium, Vascular - drug effects Enzyme-Linked Immunosorbent Assay Female Flow Cytometry ICAM-1 Immunohistochemistry Inflammation - immunology Inflammation - pathology Inflammation - prevention & control Intercellular Adhesion Molecule-1 - biosynthesis Intercellular Adhesion Molecule-1 - drug effects Mice Neurokinin-1 Receptor Antagonists NK-1 receptor Substance P Substance P - immunology T-Lymphocytes - drug effects Vascular Cell Adhesion Molecule-1 - biosynthesis Vascular Cell Adhesion Molecule-1 - drug effects VCAM-1 |
title | Suppression of autoimmune encephalomyelitis by a neurokinin-1 receptor antagonist — A putative role for substance P in CNS inflammation |
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