The influence of the proinflammatory cytokine, osteopontin, on autoimmue demyelinating desease

D. Chabas, S. E. Baranzini, D. Mitchell, C. C A Bernard, S. R. Rittling, D. T. Denhardt, R. A. Sobel, C. Lock, M. Karpuj, R. Pedotti, R. Heller, J. R. Oksenberg, L. Steinman

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Abstract

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-γ 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.

Original languageEnglish
Pages (from-to)1731-1735
Number of pages5
JournalScience
Volume294
Issue number5547
DOIs
Publication statusPublished - Nov 23 2001

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    Chabas, D., Baranzini, S. E., Mitchell, D., Bernard, C. C. A., Rittling, S. R., Denhardt, D. T., Sobel, R. A., Lock, C., Karpuj, M., Pedotti, R., Heller, R., Oksenberg, J. R., & Steinman, L. (2001). The influence of the proinflammatory cytokine, osteopontin, on autoimmue demyelinating desease. Science, 294(5547), 1731-1735. https://doi.org/10.1126/science.1062960