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

343 Citations (Scopus)

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 1996
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 9
Interferons
T-Lymphocytes
Multiple Sclerosis
Matrix Metalloproteinases
Fibronectins
Central Nervous System
Oligodendroglia
T-Lymphocyte Subsets
Therapeutics
Myelin Sheath
In Vitro Techniques
Basement Membrane
Natural Killer Cells
Pharmaceutical Preparations
Endothelium
Flow Cytometry
Western Blotting
Lymphocytes
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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

Interferon β-1b decreases the migration of T lymphocytes in vitro : Effects on matrix metalloproteinase-9. / Stüve, Olaf; Dooley, Nora P.; Uhm, Joon H.; Antel, Jack P.; Francis, Gordon S.; Williams, Gary; Yong, Voon Wee.

In: Annals of Neurology, Vol. 40, No. 6, 12.1996, p. 853-863.

Research output: Contribution to journalArticle

Stüve, O, Dooley, NP, Uhm, JH, Antel, JP, Francis, GS, Williams, G & Yong, VW 1996, 'Interferon β-1b decreases the migration of T lymphocytes in vitro: Effects on matrix metalloproteinase-9', Annals of Neurology, vol. 40, no. 6, pp. 853-863. https://doi.org/10.1002/ana.410400607
Stüve, Olaf ; Dooley, Nora P. ; Uhm, Joon H. ; Antel, Jack P. ; Francis, Gordon S. ; Williams, Gary ; Yong, Voon Wee. / Interferon β-1b decreases the migration of T lymphocytes in vitro : Effects on matrix metalloproteinase-9. In: Annals of Neurology. 1996 ; Vol. 40, No. 6. pp. 853-863.
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