Prostanoid Receptor Subtypes and Its Endogenous Ligands with Processing Enzymes within Various Types of Inflammatory Joint Diseases.

Mohammed A Al-Madol,Rudolf Likar,Reham Said Ebied,Mohammed Shaqura,Sascha Treskatsch,Magdi M Salih,Thilo John,Michael Schäfer,Shaaban A Mousa,Sandra Helena Penha Oliveira

doi:10.1155/2020/4301072

Abstract

A complex inflammatory process mediated by proinflammatory cytokines and prostaglandins commonly occurs in the synovial tissue of patients with joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). This study systematically investigated the distinct expression profile of prostaglandin E2 (PGE2), its processing enzymes (COX-2), and microsomal PGES-1 (mPGES-1) as well as the corresponding prostanoid receptor subtypes (EP1-4) in representative samples of synovial tissue from these patients (JT, OA, and RA). Quantitative TaqMan®-PCR and double immunofluorescence confocal microscopy of synovial tissue determined the abundance and exact immune cell types expressing these target molecules. Our results demonstrated that PGE2 and its processing enzymes COX-2 and mPGES-1 were highest in the synovial tissue of RA, followed by the synovial tissue of OA and JT patients. Corresponding prostanoid receptor, subtypes EP3 were highly expressed in the synovium of RA, followed by the synovial tissue of OA and JT patients. These proinflammatory target molecules were distinctly identified in JT patients mostly in synovial granulocytes, in OA patients predominantly in synovial macrophages and fibroblasts, whereas in RA patients mainly in synovial fibroblasts and plasma cells. Our findings show a distinct expression profile of EP receptor subtypes and PGE2 as well as the corresponding processing enzymes in human synovium that modulate the inflammatory process in JT, OA, and RA patients.

Highlights

Arthritis describes an inflammatory process of a joint which mainly affects the synovial tissue leading to tissue damage and fibrosis [1, 2]
Our light microscopic analysis of synovial tissues showed that lining-layer thickness, overall cellularity, and vascularity were significantly increased in rheumatoid arthritis (RA), OA, and joint trauma (JT) patients compared to control (P < 0:05, oneway analysis of variance (ANOVA) followed by Tukey’s test) (Table 1)
This study systematically investigated potential differences in the abundance of PGE-2, its processing enzymes COX-2 and microsomal PGES-1 (mPGES-1), and its corresponding prostanoid receptor subtypes EP1-4 within the synovial tissue of JT, OA, and RA patients in direct comparison to each other and to controls who underwent a diagnostic arthroscopy

Summary

Introduction

Arthritis describes an inflammatory process of a joint which mainly affects the synovial tissue leading to tissue damage and fibrosis [1, 2] It is very complex and can occur in multiple different ways, e.g., as a consequence of joint trauma (JT), as a leading cause of osteoarthritis (OA), or as a trigger for the autoimmune disease rheumatoid arthritis (RA) [1]. This process is driven by various inflammatory mediators such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and macrophage-colony stimulating factor, as well as prostaglandin E2 (PGE2) and its processing enzyme cyclooxygenase 2 (COX2) [3]. The involvement of the different prostanoid receptors EP1-EP4 and their ligands such as prostaglandin E2 (PGE2) as well as their processing enzymes COX2 and mPGES-1 has not been systematically investigated.

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Results

Conclusion