Effect of nimesulide on glucocorticoid receptor activity in human synovial fibroblasts.
Fibroblasts from human synovial membranes were cultured with nimesulide, naproxen or dexamethasone. Nimesulide, but not naproxen, showed effects on the glucocorticoid system that may contribute importantly to its anti-inflammatory activity. Nimesulide at therapeutically relevant concentrations induced the intracellular phosphorylation and activation of glucocorticoid receptors, and activated their binding to the target genes. Naproxen or dexamethasone markedly reduced the number of glucocorticoid receptor binding sites, in contrast to nimesulide, which had no significant effect.
Pelletier
J P
JP
Université de Montréal and Unité de recherche en arthrose, Centre de recherche, Centre Hospitalier de l'Université de Montréal, Québec, Canada.
Di Battista
J A
JA
Zhang
M
M
Fernandes
J
J
Alaaeddine
N
N
Martel-Pelletier
J
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects*; D008565:Membrane Proteins; D010766:Phosphorylation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*; D013583:Synovial Membrane / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011965:Receptors, Glucocorticoid; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C012655:nimesulide