THE REDUCED EXPRESSION OF GLUCOCORTICOID RECEPTORS IN SYNOVIAL-CELLS INDUCED BY NONSTEROIDAL ANTIINFLAMMATORY DRUGS CAN BE REVERSED BY PROSTAGLANDIN E(1) ANALOG

Objective. We examined the effect of 3 commonly used nonsteroidal anti inflammatory drugs (NSAID), indomethacin, naproxen and tiaprofenic aci d, and a prostaglandin E(1) analog, misoprostol, on the glucocorticoid receptor level in synovial fibroblasts. Methods. Synovial fibroblasts were isolated by enzymatic digestion from human normal synovial membr anes. These cells were incubated with therapeutic and pharmacological concentrations of NSAID in the presence or absence of misoprostol (0.1 -100 ng/ml). The glucocorticoid receptor (GR) level was measured by bi nding assay using H-3-dexamethasone. Results. Naproxen and indomethaci n but not tiaprofenic acid, at therapeutic concentrations, significant ly reduced the level of GR in synovial cells. This effect was reversed with the addition of misoprostol. Conclusion. Our findings bring insi ght into the differential effects of NSAID on the GR system and may pr ovide an explanation for the reduced level of GR found in OA chondrocy tes. The possible interference with the action of therapeutically admi nistered corticosteroids is discussed.