The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease.
Multiple sclerosis is a demyelinating disease, characterized by inflammation in the brain and spinal cord, possibly due to autoimmunity. Large-scale sequencing of cDNA libraries, derived from plaques dissected from brains of patients with multiple sclerosis (MS), indicated an abundance of transcripts for osteopontin (OPN). Microarray analysis of spinal cords from rats paralyzed by experimental autoimmune encephalomyelitis (EAE), a model of MS, also revealed increased OPN transcripts. Osteopontin-deficient mice were resistant to progressive EAE and had frequent remissions, and myelin-reactive T cells in OPN-/- mice produced more interleukin 10 and less interferon-gamma than in OPN+/+ mice. Osteopontin thus appears to regulate T helper cell-1 (TH1)-mediated demyelinating disease, and it may offer a potential target in blocking development of progressive MS.
Chabas
D
D
Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, B002, Stanford, CA 94305, USA.
Baranzini
S E
SE
Mitchell
D
D
Bernard
C C
CC
Rittling
S R
SR
Denhardt
D T
DT
Sobel
R A
RA
Lock
C
C
Karpuj
M
M
Pedotti
R
R
Heller
R
R
Oksenberg
J R
JR
Steinman
L
L
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020224:Expressed Sequence Tags; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015723:Gene Library; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012795:Sialoglycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology
D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; C506897:Spp1 protein, rat; D053495:Osteopontin; D016753:Interleukin-10; D007371:Interferon-gamma