title: Cytosolic phospholipase A2 plays a key role in the pathogenesis of multiple sclerosis-like disease.
abstract: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that results in motor and sensory deficits. Although MS and its animal model, experimental autoimmune encephalomyelitis (EAE), are thought to be T cell-mediated diseases, the mechanisms underlying the lesions in the CNS are not fully understood. We propose that a strong candidate as a central mediator in evoking the complex pathological changes seen in MS and EAE is the enzyme cytosolic phospholipase A2 (cPLA2). One of the metabolic products of this enzyme is pro-inflammatory, while the other induces myelin breakdown, demyelination, and chemokine/cytokine expression. We provide evidence that cPLA2 is highly expressed in EAE lesions and show that blocking this enzyme leads to a remarkable reduction in the onset and progression of EAE.
authors.affiliation: Centre for Research in Neuroscience, The Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada.
authors.forename: Athena
authors.initials: A
authors.lastname: Kalyvas
authors.forename: Samuel
authors.initials: S
authors.lastname: David
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000627:therapeutic use; D001369:Axons / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology; D002452:Cell Count; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2; D003583:Cytokinins / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000201:enzymology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007527:Isoenzymes / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013116:Spinal Cord / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D013997:Time Factors
chemical_list: D001095:Arachidonic Acids; D018925:Chemokines; D003583:Cytokinins; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D019707:Receptors, Chemokine; C081565:arachidonyltrifluoromethane; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2