Increased expression of B cell-associated regulatory cytokines by glatiramer acetate in mice with experimental autoimmune encephalomyelitis.
B cells are of increasing importance as a target for multiple sclerosis treatment. Here we show that GA treatment of mice with experimental autoimmune encephalomyelitis (EAE) biases cytokine production by B cells towards cytokines associated with regulation in MS including interleukin (IL)-4, -10 and -13 and reduces pro-inflammatory IL-6, IL-12, and TNF alpha levels. GA also down-regulates expression of B cell-activating factor (BAFF) of the TNF family and a proliferation-inducing ligand (APRIL), as well as the BAFF receptor in mice with EAE. Thus, GA impacts both B cell survival and B cell cytokine production during CNS inflammatory disease in an EAE model.
Begum-Haque
Sakhina
S
Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756, USA; Multiple Sclerosis Center at Dartmouth College, Lebanon, NH 03756, USA. Sakhina.begum-haque@dartmouth.edu
Sharma
Alok
A
Christy
Marc
M
Lentini
Tim
T
Ochoa-Reparaz
Javier
J
Fayed
Islam F
IF
Mielcarz
Daniel
D
Haque
Azizul
A
Kasper
Lloyd H
LH
D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects; D001921:Brain / Q000473:pathology; D018956:CD5 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D000068717:Glatiramer Acetate; D006023:Glycoproteins; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000473:pathology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism
D018941:Antigens, CD19; D053264:B-Cell Activating Factor; D018956:CD5 Antigens; D016207:Cytokines; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010455:Peptides; D012333:RNA, Messenger; C505720:Tnfsf13b protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; C445081:myelin oligodendrocyte glycoprotein (35-55); D000068717:Glatiramer Acetate