Interferon beta-1b decreases the migration of T lymphocytes in vitro: effects on matrix metalloproteinase-9.
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 beta-1b (IFNbeta-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, IFNbeta-1b reduced the migratory rate to that of unactivated T cells. In contrast, IFNgamma at 1,000 IU/ml, which caused a similar decrease (25%) in the proliferation rate of T lymphocytes as IFNbeta-1b, did not affect migration. All T-lymphocyte subsets and natural killer (NK) cells were demonstrated by flow cytometry to be equally affected by IFNbeta-1b treatment. 125I-Western blot analyses revealed that IFNbeta-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 IFNbeta-1b. We suggest that the clinical benefits of IFNbeta-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.
Stüve
O
O
Neuroimmunology Unit, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Quebec, Canada.
Dooley
N P
NP
Uhm
J H
JH
Antel
J P
JP
Francis
G S
GS
Williams
G
G
Yong
V W
VW
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D017364:Collagenases / Q000378:metabolism*; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology; D020780:Matrix Metalloproteinase 9; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology
D000276:Adjuvants, Immunologic; D000068576:Interferon beta-1b; D016899:Interferon-beta; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D000068556:Interferon beta-1a