title: Aurothiomalate inhibits the expression of mPGES-1 in primary human chondrocytes.
abstract: OBJECTIVE
  Microsomal prostaglandin E synthase-1 (mPGES-1) is a terminal enzyme in the production of prostaglandin E2 (PGE2) and its expression is upregulated during inflammation. mPGES-1 is considered as a potential drug target for the treatment of arthritis to reduce adverse effects related to the current non-steroidal anti-inflammatory drugs (NSAIDs). Our aim was to study the expression of mPGES-1 in primary human chondrocytes and whether the expression is affected by clinically used antirheumatic drugs.
  
  
  METHODS
  Primary human chondrocytes were isolated from cartilage samples obtained from patients undergoing total knee replacement surgery. Expression of mPGES-1 was studied by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis. PGE2 levels were measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  mPGES-1 expression in primary human chondrocytes was enhanced when the cells were exposed to interleukin-1β (IL-1β) and mPGES-1 protein levels continued to increase up to the 96-h follow-up. Aurothiomalate inhibited mPGES-1 expression and PGE2 production in a dose-dependent manner, as did the anti-inflammatory steroid dexamethasone. Other disease-modifying antirheumatic drugs (DMARDs) studied (sulfasalazine, methotrexate, and hydroxychloroquine) did not alter mPGES-1 expression.
  
  
  CONCLUSIONS
  The results introduce aurothiomalate as the first, and so far the only, DMARD found to be able to inhibit mPGES-1 expression. The effect is likely involved in the mechanisms of action of this gold-containing DMARD in rheumatic diseases. The results are implicated in the regulatory mechanisms of mPGES-1 expression, which are under intensive research.
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital , Tampere , Finland.
authors.forename: L
authors.initials: L
authors.lastname: Tuure
authors.forename: M
authors.initials: M
authors.lastname: Hämäläinen
authors.forename: T
authors.initials: T
authors.lastname: Moilanen
authors.forename: E
authors.initials: E
authors.lastname: Moilanen
mesh_terms: D018501:Antirheumatic Agents / Q000494:pharmacology*; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology; D020370:Osteoarthritis, Knee / Q000188:drug therapy; D061251:Primary Cell Culture; D000071876:Prostaglandin-E Synthases; D060888:Real-Time Polymerase Chain Reaction; D012460:Sulfasalazine / Q000494:pharmacology
chemical_list: D018501:Antirheumatic Agents; D005938:Glucocorticoids; D006052:Gold Sodium Thiomalate; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D003907:Dexamethasone; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; D008727:Methotrexate