| Autor: |
Asano, Kazuhito, Sakai, Misako, Matsuda, Takako, Tanaka, Hironori, Fujii, Keigo, Hisamitsu, Tadashi |
| Zdroj: |
Journal of Pharmacy and Pharmacology; March 2006, Vol. 58 Issue: 3 p359-366, 8p |
| Abstrakt: |
The aim of this study was to evaluate the influence of meloxicam on the production of both matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) from human synovial fibroblasts by TNF-α stimulation in-vitro. Synovial fibroblasts (2 times 104cells/mL) derived from patients with osteoarthritis were stimulated with 20.0 ng mL−1TNF-α in the presence of various concentrations of meloxicam. After 24 h, the culture supernatants were obtained and assayed for MMP-1, MMP-2, MMP-3, MMP-13, TIMP-1 and TIMP-2 by ELISA. mRNA expression for MMPs and TIMPs in 4-h-cultured cells were examined by real-time polymerase chain reaction. Transcriptional factor (NF-κB and AP-1) activation in 2-h-cultured cells was also examined by ELISA. Meloxicam could suppress MMP production in a dose-dependent manner. The minimum concentration of the agent that showed significant suppression was 0.6 times 10−6mfor MMP-1, MMP-2 and MMP-3, and 1.3 times 10−6mfor MMP-13. The ability of synovial fibroblasts to produce TIMPs was also suppressed by meloxicam as in the case of MMP production. Addition of meloxicam into synovial fibroblast cultures inhibited dose-dependently mRNA expression for MMPs and TIMPs, which were increased by TNF-α stimulation, through the suppression of NF-κB and AP-1 activation. The suppressive effect of meloxicam on the production of MMPs and TIMPs may partly be involved in attenuation of the clinical conditions of osteoarthritis and rheumatoid arthritis. |
| Databáze: |
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