T-614 alters the production of matrix metalloproteinases (MMP-1 andMMP-3) and inhibits the migratory expansion of rheumatoid synovial fibroblasts, in vitro.
Int Immunopharmacol
; 13(1): 54-60, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-22446297
ABSTRACT
Matrix metalloproteinases (MMPs) have a pivotal role in the destruction of cartilage in rheumatoid arthritis (RA) joint, which is mainly produced by fibroblast-like synoviocytes (FLS). T-614 is effective for patients with active RA, however the mechanism has not been clarified. We first focus on the MMPs level in RA patients after T-614 treatment, in vivo. Eighty-six RA patients were assigned into 3 treatment groups randomly T-614 group 1 (T-614 for the first 4 weeks with an oral dosage of 25mg once daily, and 50mg/day for the subsequent 20 weeks with an oral dosage of 25mg twice daily), T-614 group 2 (T-614 with an oral dosage of 25mg twice daily), or the MTX group (MTX 10 mg/week orally for the first 4 weeks and 15 mg/week for the subsequent 20 weeks). Serum samples were obtained at 0 and 24 weeks. Levels of MMP-1 and MMP-3 were decreased significantly after 24 week treatment of T-614 group 2 or MTX group. In vitro, RA FLS were pretreated with different doses of T-614 and then stimulated with TNF-α, IL-1ß or IL-17A, respectively. Protein and mRNA levels of MMP-1 and MMP-3 were further determined. MMP-1 production was significantly inhibited at 50 µg/ml T-614 and MMP-3 production was significantly inhibited at 5 µg/ml or more T-614. The mRNA expression profile was in accordance with the protein production. Inhibition of invasiveness was also seen after T-614 treatment. These results suggest that T-614 inhibits the invasiveness through decreasing the MMP-1 and MMP-3 production.
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MEDLINE
Assunto principal:
Artrite Reumatoide
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Sulfonamidas
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Membrana Sinovial
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Benzopiranos
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Movimento Celular
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Anti-Inflamatórios não Esteroides
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Metaloproteinase 3 da Matriz
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Metaloproteinase 1 da Matriz
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Fibroblastos
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article