| Autor: |
Pillinger, Michael H., Dinsell, Victoria, Apsel, Beth, Tolani, Sonia N., Marjanovic, Nada, Chan, Edwin S.L., Gomez, Paul, Clancy, Robert, Chang, Lih-Fan, Abramson, Steven B. |
| Předmět: |
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| Zdroj: |
British Journal of Pharmacology; Jul2004, Vol. 142 Issue 6, p973-982, 10p |
| Abstrakt: |
1. Nabumetone is a prodrug that is converted in vivo into 6-methoxy-2-naphthylacetic acid (6MNA), a cyclooxygenase inhibitor with anti-inflammatory properties. We tested the effects of nabumetone and 6MNA on the inflammatory responses of synovial fibroblasts (SFs). 2 Brief exposures to 6MNA (50-150 μM) had no effect on IL-1β/TNF-α (each 20 ng ml-1)-stimulated Erk activation. Longer exposures depleted prostaglandin Ei (PGE1) as much as 70%, and stimulated Erk as much as 300%. Nabumetone (150 μM) inhibited Erk activation by 60-80%. 3. 6MNA (50-150 μM) stimulated (≈ 200%) and nabumetone (150 μM) inhibited (≈ 50%) matrix metalloproteinase (MMP)-1, but not MMP-13 secretion from SFs. 6MNA stimulation of MMP-1 secretion was inhibited ≈ 30% by PGE1 (1 μM) and ≈ 80% by the Erk pathway inhibitor UO126 (10 μM), confirming that PGE depletion and Erk activation mediate MMP-1 secretion by 6MNA. 4. Consistent with its role as an Erk inhibitor, nabumetone (150 μM) abrogated 6MNA enhancement of MMP-1 secretion. 5 UO126 (10 μM) and nabumetone (150 μM) inhibited (≈ 70 and 40%, respectively), but 6MNA (150 μM) enhanced (≈ 40%). NF-κB activation. 6. Our data indicate that 6MNA shares with other COX inhibitors several proinflammatory effects on synovial fibroblasls. In contrast, nabumetone demonstrates anti-inflammatory and potentially arthroprotective effects that have not been previously appreciated. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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