Department of Anaesthesiology and Intensive Care Medicine, Charité-University Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany.
Department for Orthopedic and Trauma Surgery, DRK Kliniken Berlin Westend, Berlin, Germany.
Mediators Inflamm. 2020 Nov 12;2020:4301072. doi: 10.1155/2020/4301072. eCollection 2020.
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.
一种由促炎细胞因子和前列腺素介导的复杂炎症过程，通常发生在患有关节创伤 (JT)、骨关节炎 (OA) 和类风湿关节炎 (RA) 的患者的滑膜组织中。本研究系统地研究了前列腺素 E2 (PGE2)、其代谢酶 (COX-2) 和微粒体 PGES-1 (mPGES-1) 以及相应的前列腺素受体亚型 (EP1-4) 在这些患者的滑膜组织代表性样本中的独特表达谱 (JT、OA 和 RA)。定量 TaqMan®-PCR 和滑膜组织双免疫荧光共聚焦显微镜确定了这些靶分子的丰度和确切的免疫细胞类型。我们的结果表明，PGE2 及其代谢酶 COX-2 和 mPGES-1 在 RA 的滑膜组织中表达最高，其次是 OA 和 JT 患者的滑膜组织。相应的前列腺素受体亚型 EP3 在 RA 的滑膜中高度表达，其次是 OA 和 JT 患者的滑膜组织。这些促炎靶分子在 JT 患者的滑膜中主要在滑膜粒细胞中被明显识别，在 OA 患者的滑膜中主要在滑膜巨噬细胞和成纤维细胞中被识别，而在 RA 患者的滑膜中主要在滑膜成纤维细胞和浆细胞中被识别。我们的研究结果表明，在人类滑膜中，EP 受体亚型和 PGE2 以及相应的代谢酶的表达谱存在明显差异，这些差异调节了 JT、OA 和 RA 患者的炎症过程。
