Selective matrix metalloproteinase inhibitor, N-biphenyl sulfonyl phenylalanine hydroxamic acid, inhibits the migration of CD4+ T lymphocytes in patients with HTLV-I-associated myelopathy.
Matrix metalloproteinases (MMPs) have been reported to be involved in various inflammatory disorders. Previous studies revealed that MMP-2 and MMP-9 might play important roles in the breakdown of the blood-brain barrier (BBB) in the central nervous system (CNS) of patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). N-Biphenyl sulfonyl-phenylalanine hydroxamic acid (BPHA) selectively inhibits MMP-2, -9 and -14, but not MMP-1, -3 and -7. In the present study, we examined whether or not the selective MMP inhibitor BPHA could inhibit the heightened migrating activity of CD4+ T cells in HAM/TSP patients. The migration assay using an invasion chamber showed that migration of CD4+ T cells in HAM/TSP patients was inhibited by 25 microM BPHA. In addition, the inhibitory ratio of migrating CD4+ lymphocytes was higher in HAM patients compared to normal controls. These results suggest that the selective MMP inhibitor BPHA has therapeutic potential for HAM/TSP.
Ikegami
Mayumi
M
The Third Department of Internal Medicine, Kagoshima University, School of Medicine, Sakuragaoka 8-35-1, 890 Kagoshima, Japan.
Umehara
Fujio
F
Ikegami
Naohito
N
Maekawa
Ryuji
R
Osame
Mitsuhiro
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001672:Biocompatible Materials; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003094:Collagen; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007797:Laminin; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology*; D011509:Proteoglycans
D001672:Biocompatible Materials; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; C400001:N-biphenylsulfonylphenylalanine hydroxamic acid; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D020780:Matrix Metalloproteinase 9