title: Glatiramer acetate biases dendritic cells towards an anti-inflammatory phenotype by modulating OPN, IL-17, and RORγt responses and by increasing IL-10 production in experimental allergic encephalomyelitis.
abstract: Paralleling our previous mechanistic studies of glatiramer acetate (GA; Copaxone) activity, we show that GA curbs the expression of Toll-like receptor (TLR) 9 and the universal adapter protein Myd88 in mice with EAE, the animal model for multiple sclerosis. Concurrent with enhanced dendritic cell (DC) production of IL-10, GA interferes with OPN, IL-17, and ROR gamma expression in DCs of mice with EAE, and suppresses brain expression of the EAE-induced chemokines, MIP1α and β, IP-10 and RANTES. Thus GA not only biases dendritic cells towards an anti-inflammatory phenotype, but also suppresses the expression of factors that affect the blood-brain barrier penetration during neuroinflammation.
authors.affiliation: Department of Neurology, Geisel Medical School at Dartmouth, Lebanon, NH 03756, USA. Sakhina.Begum-Haque@Dartmouth.EDU
authors.forename: Sakhina
authors.initials: S
authors.lastname: Begum-Haque
authors.forename: Marc
authors.initials: M
authors.lastname: Christy
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Eli
authors.initials: E
authors.lastname: Kasper
authors.forename: Javier
authors.initials: J
authors.lastname: Ochoa-Reparaz
authors.forename: Jacqueline Y
authors.initials: JY
authors.lastname: Smith
authors.forename: Azizul
authors.initials: A
authors.lastname: Haque
authors.forename: Lloyd H
authors.initials: LH
authors.lastname: Kasper
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D000068717:Glatiramer Acetate; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051193:Toll-Like Receptors / Q000235:genetics
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010455:Peptides; D051193:Toll-Like Receptors; D053495:Osteopontin; D016753:Interleukin-10; D000068717:Glatiramer Acetate