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Suppression of autoimmune encephalomyelitis by a neurokinin-1 receptor antagonist--a putative role for substance P in CNS inflammation.
Suppression of autoimmune encephalomyelitis by a neurokinin-1 receptor antagonist--a putative role for substance P in CNS inflammation.
- Source :
-
Journal of neuroimmunology [J Neuroimmunol] 2006 Oct; Vol. 179 (1-2), pp. 1-8. Date of Electronic Publication: 2006 Aug 10. - Publication Year :
- 2006
-
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.
- Subjects :
- Adoptive Transfer
Animals
Blood-Brain Barrier drug effects
Central Nervous System immunology
Central Nervous System pathology
Cytokines drug effects
Cytokines metabolism
Encephalomyelitis, Autoimmune, Experimental immunology
Encephalomyelitis, Autoimmune, Experimental pathology
Endothelium, Vascular drug effects
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Immunohistochemistry
Inflammation immunology
Inflammation pathology
Inflammation prevention & control
Intercellular Adhesion Molecule-1 biosynthesis
Intercellular Adhesion Molecule-1 drug effects
Mice
T-Lymphocytes drug effects
Vascular Cell Adhesion Molecule-1 biosynthesis
Vascular Cell Adhesion Molecule-1 drug effects
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Biphenyl Compounds pharmacology
Central Nervous System drug effects
Encephalomyelitis, Autoimmune, Experimental prevention & control
Neurokinin-1 Receptor Antagonists
Substance P immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0165-5728
- Volume :
- 179
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Journal of neuroimmunology
- Publication Type :
- Academic Journal
- Accession number :
- 16904192
- Full Text :
- https://doi.org/10.1016/j.jneuroim.2006.06.026