%0 Journal Article
%T Limited effect of anti-rheumatic treatment on 15-prostaglandin dehydrogenase in rheumatoid arthritis synovial tissue
%A Karina Gheorghe
%A Syed Sadique
%A Patrick Leclerc
%A Helena Idborg
%A Ivonne Wobst
%A Anca Catrina
%A Per-Johan Jakobsson
%A Marina Korotkova
%J Arthritis Research & Therapy
%D 2012
%I BioMed Central
%R 10.1186/ar3851
%X 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) 1¦Â-activated fibroblast-like synoviocytes (FLS) treated with methotrexate.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.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.Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and extensive proliferation within the joint synovial tissue and by recruitment and activation of immune cells and subsequent cartilage and bone destruction. Rheumatoid joint displays an activated prostaglandin E2 (PGE2) pathway, and there are high levels of this mediator in the synovial fluid and strong expression in the synovium of its synthesizing enzymes, microsomal prostaglandin E2 synthase 1 (mPGES-1) as well as cyclooxygenase (COX) 1 and 2 [1]. Wheres COX-1 is considered a constitutive enzyme present under basal conditions, COX-2 is inflammation-induced [2] and co-localizes with mPGES-1 in the synovial
%U http://arthritis-research.com/content/14/3/R121