Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular chondrocytes.

作者：Francisco Javier Blanco, Ramón Guitián, Juan Jose Moreno, F J de Toro, F. Galdo · 发表于：PubMed · 年份：1999 · 被引用次数：120 · 研究领域：Inflammatory mediators and NSAID effects、Osteoarthritis Treatment and Mechanisms、Connective Tissue Growth Factor Research

OBJECTIVE: To study the effect of steroidal and nonsteroidal antiinflammatory drugs (NSAID) on cyclooxygenase (COX-1 and COX-2) activity in human articular chondrocytes. METHODS: Chondrocytes were isolated from articular cartilage of donors with no articular disease. Unstimulated and interleukin 1 (IL-1) stimulated chondrocytes were used as models to study the effects of drugs on COX-1 and COX-2. Cells were incubated with vehicle or drugs; supernatants were removed and the level of prostaglandin E2 (PGE2) in each sample was determined by enzyme immunoassay. IC50 were calculated from the reduction in PGE2 content by different concentrations of the test substance by linear regression analysis. RESULTS: COX- mRNA was detected in unstimulated cells, but stimulation with IL-1 for up 12 h did not modify the levels of COX-1 mRNA. In contrast, COX-2 mRNA was not detectable in unstimulated cells, but it was induced by IL-1. Dexamethasone inhibited COX-2 mRNA expression induced by IL-1. COX-2 protein levels correlated with mRNA expression. Dexamethasone was the strongest drug inhibitor of COX-2 (IC50 = 0.0073 microM). However, it did not inhibit COX-1 activity. Among all NSAID tested, meloxicam and aspirin were the least potent inhibitors of COX-1 (IC50 = 36.6 microM and 3.57 microM, respectively). Indomethacin and diclofenac were the most potent inhibitors of COX-1 (IC50 = 0.063 microM and 0.611 microM, respectively) and COX-2 isoforms (IC50 = 0.48 microM and IC50 = 0.63 microM, respe...