Antiasthmatic Drugs Targeting the Cysteinyl Leukotriene Receptor 1 Alleviate Central Nervous System Inflammatory Cell Infiltration and Pathogenesis of Experimental Autoimmune Encephalomyelitis
Open Access
- 1 September 2011
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 187 (5), 2336-2345
- https://doi.org/10.4049/jimmunol.1100333
Abstract
Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators and are considered to play a key role in inflammatory diseases such as asthma. Antagonists targeting the receptor of CysLTs (CysLT1) are currently used as antiasthmatic drugs. CysLTs have also been implicated in other inflammatory reactions. In this study, we report that in experimental autoimmune encephalomyelitis animals, CysLT1 is upregulated in immune tissue and the spinal cord, and CysLT levels in the blood and cerebrospinal fluid are also higher than in normal mice. Two clinically used antiasthma drugs, montelukast and zafirlukast, both targeting CysLT1, effectively block the CNS infiltration of inflammatory cells and thus reduce the incidence, peak severity, and cumulative clinical scores. Further study indicated that CysLT1 signaling does not affect the differentiation of pathogenic T helper cells. It might affect the pathogenesis of experimental autoimmune encephalomyelitis by increasing the secretion of IL-17 from myelin oligodendrocyte glycoprotein-specific T cells, increasing the permeability of the blood–brain barrier and inducing chemotaxis of T cells. These effects can be blocked by CysLT1 antagonists. Our findings indicate that the antiasthmatic drugs against CysLT1 can also be used to treat multiple sclerosis.Keywords
This publication has 53 references indexed in Scilit:
- Blood–brain barrier disruption and enhanced vascular permeability in the multiple sclerosis model EAEJournal of Neuroimmunology, 2010
- Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosisNature Medicine, 2009
- T Cell-Mediated Autoimmune Disease Due to Low-Affinity Crossreactivity to Common Microbial PeptidesImmunity, 2009
- Blood–brain barrier changes and cell invasion differ between therapeutic immune clearance of neurotrophic virus and CNS autoimmunityProceedings of the National Academy of Sciences, 2008
- Urinary leukotriene E4 excretion: A biomarker of inflammatory bowel disease activityInflammatory Bowel Diseases, 2008
- Cysteinyl leukotriene receptor CysLT1as a novel therapeutic target for allergic rhinitis treatmentEmerging Therapeutic Targets, 2008
- The Effect of Montelukast and Low-Dose Theophylline on Cardiovascular Disease Risk Factors in AsthmaticsChest, 2007
- Molecular mechanisms involved in T cell migration across the blood–brain barrierJournal of Neural Transmission, 2006
- Cysteinyl Leukotrienes Regulate Dendritic Cell Functions in a Murine Model of AsthmaThe Journal of Immunology, 2004
- Cysteinyl leukotrienes in asthma: old mediators up to new tricksTrends in Pharmacological Sciences, 1995