Effect of nimesulide on glucocorticoid receptor activity in human synovialfibroblasts

Fibroblasts from human synovial membranes were cultured with nimesulide, na proxen or dexamethasone. Nimesulide, but not naproxen, showed effects on th e glucocorticoid system that may contribute importantly to its anti-inflamm atory activity. Nimesulide at therapeutically relevant concentrations induc ed the intracellular phosphorylation and activation of glucocorticoid recep tors, and activated their binding to the target genes. Naproxen or dexameth asone markedly reduced the number of glucocorticoid receptor binding sites, in contrast to nimesulide, which had no significant effect.