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

Olaf Stüve, Nora P. Dooley, Joon H. Uhm, Jack P. Antel, Gordon S. Francis, Gary Williams, Voon Wee Yong

Research output: Contribution to journalArticle

346 Scopus citations

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 oft lymphocytes as 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-Western blot 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.

Original languageEnglish (US)
Pages (from-to)853-863
Number of pages11
JournalAnnals of neurology
Volume40
Issue number6
DOIs
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Stüve, O., Dooley, N. P., Uhm, J. H., Antel, J. P., Francis, G. S., Williams, G., & Yong, V. W. (1996). Interferon β-1b decreases the migration of T lymphocytes in vitro: Effects on matrix metalloproteinase-9. Annals of neurology, 40(6), 853-863. https://doi.org/10.1002/ana.410400607