K Vuolteenaho1, P Kujala, T Moilanen, E Moilanen. 1. The Immunopharmacological Research Group, Medical School, University of Tampere, Tampere University Hospital, Finland.
Abstract
OBJECTIVES: Nitric oxide (NO) is a destructive mediator produced by activated chondrocytes. The aim of the present study was to investigate the effect of disease-modifying anti-rheumatic drugs (DMARDs) on interleukin-1beta (IL-1beta)-induced NO production in chondrocyte cultures, and in human osteoarthritic cartilage. RESULTS: Aurothiomalate, hydroxychloroquine, methotrexate and leflunomide inhibited IL-1beta-induced inducible NO synthase (iNOS) expression and NO production in immortalized H4 chondrocytes, while penicillamine and sulfasalazine had no effect. This can be explained by the fact that the four effective DMARDs also suppressed IL-1beta-induced activation of nuclear factor kappa B (NF-kappaB), which is a crucial transcription factor for iNOS. Aurothiomalate and hydroxychloroquine also inhibited IL-1beta-induced NO production in OA cartilage whereas methotrexate and leflunomide had no effect. CONCLUSION: Aurothiomalate and hydroxychloroquine suppressed IL-1beta-induced NO production in chondrocyte cultures and in OA cartilage. The results suggest an additional anti-inflammatory mechanism for aurothiomalate and hydroxychloroquine and indicates their possible therapeutic value in the treatment of osteoarthritis (OA).
OBJECTIVES:Nitric oxide (NO) is a destructive mediator produced by activated chondrocytes. The aim of the present study was to investigate the effect of disease-modifying anti-rheumatic drugs (DMARDs) on interleukin-1beta (IL-1beta)-induced NO production in chondrocyte cultures, and in humanosteoarthritic cartilage. RESULTS:Aurothiomalate, hydroxychloroquine, methotrexate and leflunomide inhibited IL-1beta-induced inducible NO synthase (iNOS) expression and NO production in immortalized H4 chondrocytes, while penicillamine and sulfasalazine had no effect. This can be explained by the fact that the four effective DMARDs also suppressed IL-1beta-induced activation of nuclear factor kappa B (NF-kappaB), which is a crucial transcription factor for iNOS. Aurothiomalate and hydroxychloroquine also inhibited IL-1beta-induced NO production in OA cartilage whereas methotrexate and leflunomide had no effect. CONCLUSION:Aurothiomalate and hydroxychloroquine suppressed IL-1beta-induced NO production in chondrocyte cultures and in OA cartilage. The results suggest an additional anti-inflammatory mechanism for aurothiomalate and hydroxychloroquine and indicates their possible therapeutic value in the treatment of osteoarthritis (OA).
Authors: Sarah R Kingsbury; Puvan Tharmanathan; Joy Adamson; Nigel K Arden; Fraser Birrell; Sarah Cockayne; John Dickson; Michael Doherty; Krysia S Dziedzic; Andrew Grainger; Catherine E Hewitt; Terence W O'Neill; David L Scott; Tonia L Vincent; Richard J Wakefield; Fiona E Watt; David J Torgerson; Philip G Conaghan Journal: Trials Date: 2013-03-02 Impact factor: 2.279