Interferon β-1b decreases the migration of T lymphocytes in vitro: Effects on matrix metalloproteinase-9

Authors

  • Olaf Stüve MD,

    1. Neuroimmunology Unit, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
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  • Nora P. Dooley MSc,

    1. Neuroimmunology Unit, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
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  • Joon H. Uhm MD,

    1. Neuroimmunology Unit, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
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  • Jack P. Antel MD,

    1. Neuroimmunology Unit, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
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  • Gordon S. Francis MD,

    1. Neuroimmunology Unit, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
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  • Voon Wee Yong PhD,

    Corresponding author
    1. Neuroimmunology Unit, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
    • Departments of oncology and Clinical Neurosciences, University of Calgary, 3330 Hospital Drive, Calgary NW, Alberta T2N 4N1, Canada
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  • Gary Williams PhD

    1. Berlex Laboratories, Richmond, CA
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Abstract

In multiple sclerosis (MS), the influx of activated T lymphocytes into the brain parenchyma leads to the subsequent damage of oligodendrocytes, the cells that produce central nervous system (CNS) myelin. We report here that interferon β-1b (IFNβ-1b), a drug shown to be efficacious in the treatment of patients with MS, decreases the in vitro migration of activated T lymphocytes through fibronectin (FN), a major component of the basement membrane that surrounds cerebral endothelium. At 1,000 IU/ml, IFNβ-1b reduced the migratory rate to that of unactivated T cells. In contrast, IFNγ at 1,000 IU/ml, which caused a similar decrease (25%) in the proliferation rate of T lymphocytesas IFNβ-1b, did not affect migration. All T-lymphocyte subsets and natural killer (NK) cells were demonstrated by flow cytometry to be equally affected by IFNβ-1b treatment. 125I-Westernblot analyses revealed that IFNβ-1b treatment resulted in a marked reduction of the ability of T cells to cleave FN. The substrate-degrading capability of T lymphocytes was shown to be due predominantly to the activity of a 92-kd matrix metalloproteinase, MMP-9, whose levels were decreased by IFNβ-1b. We suggest that the clinical benefits of IFNβ-1b treatment in MS patients may be in part a result of the ability of this drug to significantly decrease MMP-9 activity, leading to a reduction of T-lymphocyte infiltration into the CNS.

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