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The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease
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Chabas, D
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Baranzini, SE
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Mitchell, D
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Bernard, CCA
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Rittling, SR
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Denhardt, DT
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Sobel, RA
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Lock, C
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Karpuj, M
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机构: Beckman Ctr Mol Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA

Pedotti, R
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机构: Beckman Ctr Mol Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA

Heller, R
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机构: Beckman Ctr Mol Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA

Oksenberg, JR
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机构: Beckman Ctr Mol Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA

Steinman, L
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机构: Beckman Ctr Mol Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA
机构:
[1] Beckman Ctr Mol Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA
[2] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA
[3] La Trobe Univ, Dept Biochem, Neuroimmunol Lab, Bundoora, Vic 3083, Australia
[4] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA
[5] Stanford Univ, Dept Pathol Neuropathol, Sch Med, Stanford, CA 94305 USA
[6] Roche Biosci, Palo Alto, CA 94304 USA
来源:
关键词:
D O I:
10.1126/science.1062960
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
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 (T(H)1)-mediated demyelinating disease, and it may offer a potential target in blocking development of progressive MS.
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页码:1731 / 1735
页数:5
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