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Aurothiomalate inhibits COX-2 expression in chondrocytes and in human cartilage possibly through its effects on COX-2

Riina Nieminen1, Katriina Vuolteenaho, Asko Riutta

  • 1The Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, Tampere, Finland.

European Journal of Pharmacology
|May 2, 2008
PubMed

Insights

Aurothiomalate, a disease-modifying anti-rheumatic drug, inhibits cyclooxygenase-2 (COX-2) expression and pro-inflammatory prostanoid production in chondrocytes. This action is mediated by enhanced COX-2 mRNA degradation, potentially via reduced HuR expression, offering a novel therapeutic mechanism for arthritis.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Rheumatology

Background:

  • Cyclooxygenase-2 (COX-2) is implicated in the inflammation associated with rheumatoid and osteoarthritis.
  • Pro-inflammatory prostanoids produced by COX-2 contribute to joint pathology.

Purpose of the Study:

  • To investigate the effects of disease-modifying anti-rheumatic drugs (DMARDs) on COX-2 expression in chondrocytes.
  • To elucidate the mechanism of action of aurothiomalate in inhibiting COX-2 expression.

Main Methods:

  • Chondrocytes were treated with IL-1beta and various DMARDs, including aurothiomalate.
  • COX-2 protein expression, PGE(2) production, and mRNA levels were assessed.
  • mRNA degradation was studied using Actinomycin D, and HuR expression was analyzed.

Main Results:

  • Aurothiomalate significantly inhibited IL-1beta-induced COX-2 protein expression and PGE(2) production in a dose-dependent manner.
  • Aurothiomalate reduced the half-life of COX-2 mRNA, indicating enhanced degradation.
  • Aurothiomalate decreased HuR expression, a key factor in mRNA stabilization.

Conclusions:

  • Aurothiomalate effectively reduces COX-2 expression and PGE(2) production in chondrocytes and human cartilage.
  • The mechanism involves accelerated COX-2 mRNA degradation, likely through reduced HuR expression.
  • This provides a novel understanding of aurothiomalate's therapeutic potential in arthritis treatment.

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