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Logo of arthrestherBioMed Centralbiomed central web sitesearchsubmit a manuscriptregisterthis articleArthritis Research & Therapy
 
Arthritis Res Ther. 2012; 14(3): R121.
Published online May 22, 2012. doi:  10.1186/ar3851
PMCID: PMC3446502
Limited effect of anti-rheumatic treatment on 15-prostaglandin dehydrogenase in rheumatoid arthritis synovial tissue
Karina Roxana Gheorghe,1 Syed Sadique,1 Patrick Leclerc,1 Helena Idborg,1 Ivonne Wobst,2 Anca Irinel Catrina,1 Per-Johan Jakobsson,1 and Marina Korotkovacorresponding author1,3
1Department of Medicine, Rheumatology Unit, Karolinska Institute/Karolinska University Hospital Solna, Stockholm, 171 76 Sweden
2Institute for Clinical Pharmacology, Johann Wolfgang Goethe-University Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt/Main, Germany
3Actar AB, Nobels väg 3, Solna, 171 65 Sweden
corresponding authorCorresponding author.
Karina Roxana Gheorghe: karina.gheorghe/at/ki.se; Syed Sadique: sayed78/at/gmail.com; Patrick Leclerc: patrick.leclerc/at/ki.se; Helena Idborg: helena.idborg/at/ki.se; Ivonne Wobst: ivimargit/at/gmx.de; Anca Irinel Catrina: anca.catrina/at/ki.se; Per-Johan Jakobsson: per-johan.jakobsson/at/ki.se; Marina Korotkova: marina.korotkova/at/ki.se
Received January 13, 2012; Revised April 20, 2012; Accepted May 22, 2012.
Abstract
Introduction
Rheumatoid arthritis (RA) is a chronic inflammatory disease in which prostaglandin E2 (PGE2) 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 PGE2. 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 PGE2 pathway 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 PGE2 synthesizing enzymes or COX-derived metabolites. Thus therapeutic strategies involving blocking induced PGE2 synthesis may find a rationale in additionally reducing local inflammatory mediators.
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