title: Antiasthmatic drugs targeting the cysteinyl leukotriene receptor 1 alleviate central nervous system inflammatory cell infiltration and pathogenesis of experimental autoimmune encephalomyelitis.
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.
authors.affiliation: Laboratory of Receptor-Based BioMedicine, School of Life Sciences and Technology, Shanghai Key Laboratory of Signaling and Disease Research, Tongji University, Shanghai 200092, China.
authors.forename: Liefeng
authors.initials: L
authors.lastname: Wang
authors.forename: Changsheng
authors.initials: C
authors.lastname: Du
authors.forename: Jie
authors.initials: J
authors.lastname: Lv
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Ye
authors.initials: Y
authors.lastname: Cui
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects; D015153:Blotting, Western; D002469:Cell Separation; D003521:Cyclopropanes; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007211:Indoles; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D048448:Phenylcarbamates; D011804:Quinolines / Q000494:pharmacology; D018077:Receptors, Leukotriene / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D013440:Sulfides; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000494:pharmacology
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D007211:Indoles; D048448:Phenylcarbamates; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; D013449:Sulfonamides; D014105:Tosyl Compounds; C083169:leukotriene D4 receptor; C093875:montelukast; C062735:zafirlukast