Limited effect of anti-rheumatic treatment on 15-prostaglandin dehydrogenase in rheumatoid arthritis synovial tissue Report as inadecuate




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Arthritis Research and Therapy

, 14:R121

First Online: 22 May 2012Received: 13 January 2012Revised: 20 April 2012Accepted: 22 May 2012

Abstract

IntroductionRheumatoid 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.

MethodsSynovial 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.

Results15-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.

ConclusionsEarly 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.

Abbreviations15-PGDH15-prostaglandin dehydrogenase

COXcyclooxygenase

DAS28Disease Activity Score in 28 joints

FLSfibroblast-like synoviocyte

GCglucocorticoid

ILinterleukin

LC-MS-MSliquid chromatography tandem mass spectrometry

mPGES-1microsomal prostaglandin E2 synthase 1

NSAIDnon-steroidal anti-inflammatory drug

OAostheoarthritis

PBSphosphate-buffered saline

PGprostaglandin

PsApsoriatic arthritis

RArheumatoid arthritis

TNFtumor necrosis factor

TTBSTris-Tween-buffered saline

Txtromboxane.

Electronic supplementary materialThe online version of this article doi:10.1186-ar3851 contains supplementary material, which is available to authorized users.

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Author: Karina Roxana Gheorghe - Syed Sadique - Patrick Leclerc - Helena Idborg - Ivonne Wobst - Anca Irinel Catrina - Per-Johan 

Source: https://link.springer.com/







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