Premium
Interferon β‐1b decreases the migration of T lymphocytes in vitro: Effects on matrix metalloproteinase‐9
Author(s) -
Stüve Olaf,
Dooley Nora P.,
Uhm Joon H.,
Antel Jack P.,
Francis Gordon S.,
Yong Voon Wee,
Williams Gary
Publication year - 1996
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410400607
Subject(s) - multiple sclerosis , matrix metalloproteinase , immunology , medicine , in vitro , fibronectin , lymphocyte , interferon beta 1b , flow cytometry , pharmacology , biology , extracellular matrix , biochemistry , interferon beta
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. 125 I‐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.