Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which prostaglandin E 2(PGE 2) displays an important pathogenic role. The enzymes involved in its synthesis are highly expressed in the inflamed synovium, while little is known about 15- prostaglandin dehydrogenase (15-PGDH) that metabolizes PGE 2. Here we aimed to evaluate the localization of 15-PGDH in the synovial tissue of healthy individuals or patients with inflammatory arthritis and determine the influence of common RA therapy on its expression.Methods: Synovial tissue specimens from healthy individuals, psoriatic arthritis, ostheoarthritis and RA patients were immunohistochemically stained to describe the expression pattern of 15-PGDH. In addition, the degree of enzyme staining was evaluated by computer analysis on stained synovial biopsies from two groups of RA patients, before and after RA specific treatment with either intra-articular glucocorticoids or oral methotrexate therapy. Prostaglandins derived from the cyclooxygenase (COX) pathway were determined by liquid-chromatography mass spectrometry in supernatants from interleukin (IL) 1β-activated fibroblast-like synoviocytes (FLS) treated with methotrexate.Results: 15-PGDH was present in healthy and inflamed synovial tissue, mainly in lining macrophages, fibroblasts and vessels. Intra-articular glucocorticoids showed a trend towards reduced 15-PGDH expression in RA synovium (p = 0.08) while methotrexate treatment left the PGE 2pathway unaltered both in biopsies ex vivo and in cultured FLS.Conclusions: Early methotrexate therapy has little influence on the expression of 15-PGDH and on any of the PGE 2synthesizing enzymes or COX-derived metabolites. Thus therapeutic strategies involving blocking induced PGE 2synthesis may find a rationale in additionally reducing local inflammatory mediators. © 2012 Gheorghe et al.; licensee BioMed Central Ltd.
CITATION STYLE
Gheorghe, K. R., Sadique, S., Leclerc, P., Idborg, H., Wobst, I., Catrina, A. I., … Korotkova, M. (2012). Limited effect of anti-rheumatic treatment on 15-prostaglandin dehydrogenase in rheumatoid arthritis synovial tissue. Arthritis Research and Therapy, 14(3). https://doi.org/10.1186/ar3851
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