title: The reduced expression of glucocorticoid receptors in synovial cells induced by nonsteroidal antiinflammatory drugs can be reversed by prostaglandin E1 analog.
abstract: OBJECTIVE
  We examined the effect of 3 commonly used nonsteroidal antiinflammatory drugs (NSAID), indomethacin, naproxen and tiaprofenic acid, and a prostaglandin E1 analog, misoprostol, on the glucocorticoid receptor level in synovial fibroblasts.
  
  
  METHODS
  Synovial fibroblasts were isolated by enzymatic digestion from human normal synovial membranes. 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 binding assay using 3H-dexamethasone.
  
  
  RESULTS
  Naproxen and indomethacin but not tiaprofenic acid, at therapeutic concentrations, significantly reduced the level of GR in synovial cells. This effect was reversed with the addition of misoprostol.
  
  
  CONCLUSIONS
  Our findings bring insight into the differential effects of NSAID on the GR system and may provide an explanation for the reduced level of GR found in OA chondrocytes. The possible interference with the action of therapeutically administered corticosteroids is discussed.
authors.affiliation: Notre-Dame Hospital Research Center, Department of Medicine, University of Montreal, PQ, Canada.
authors.forename: J P
authors.initials: JP
authors.lastname: Pelletier
authors.forename: J A
authors.initials: JA
authors.lastname: DiBattista
authors.forename: P
authors.initials: P
authors.lastname: Ranger
authors.forename: J
authors.initials: J
authors.lastname: Martel-Pelletier
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D016595:Misoprostol / Q000494:pharmacology*; D009288:Naproxen / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011422:Propionates; D011965:Receptors, Glucocorticoid; D016595:Misoprostol; C021270:tiaprofenic acid; D009288:Naproxen; D007213:Indomethacin