Potential roles of microsomal prostaglandin E synthase-1 in rheumatoid arthritis.
Potential roles of microsomal prostaglandin E synthase-1 in rheumatoid arthritis.
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DOI：
10.2492/inflammregen.31.157
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发表时间：
2011-03
影响因子：
8.1
通讯作者：
Crofford LJ
中科院分区：
文献类型：
--
作者：
Kojima F;Matnani RG;Kawai S;Ushikubi F;Crofford LJ
类风湿性关节炎（RA）是一种慢性自身免疫性疾病，主要影响滑膜关节，导致炎症、疼痛和关节畸形。非甾体抗炎药（NSAID）和糖皮质激素均抑制环氧合酶（COX），已广泛用于治疗 RA 患者。前列腺素 E 合酶 (PGES) 是一种特异性生物合成酶，作用于 COX 下游，将前列腺素 (PG) H2 转化为 PGE2。在 PGES 同工酶中，微粒体 PGES-1 (mPGES-1) 已被证明在炎症条件下在多种细胞和组织中被诱导。 RA患者滑膜组织中mPGES-1的诱导与促炎细胞因子激活组织密切相关。尽管选择性 mPGES-1 抑制剂尚未广泛应用，但已经培育出缺乏 mPGES-1 的小鼠（mPGES-1–/– 小鼠）来评估 mPGES-1 在体内的生理和病理作用。最近利用 mPGES-1–/– 小鼠的研究证明了 mPGES-1 在自身免疫性关节炎模型中慢性炎症和诱发体液免疫反应过程中的重要性。这些最新发现强调 mPGES-1 作为治疗自身免疫炎症性疾病（包括 RA）的新治疗靶点。目前，正在测试天然和合成化学品对 mPGES-1 产生 PGE2 活性的抑制作用。本综述重点介绍 mPGES-1 在 RA 病理生理学中的作用的最新进展。
Rheumatoid arthritis (RA) is a chronic autoimmune disease which primarily affects the synovial joints leading to inflammation, pain and joint deformities. Nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, both of which inhibit cyclooxygenase (COX), have been extensively used for treating RA patients. Prostaglandin E synthase (PGES) is a specific biosynthetic enzyme that acts downstream of COX and converts prostaglandin (PG) H2 to PGE2. Among PGES isozymes, microsomal PGES-1 (mPGES-1) has been shown to be induced in a variety of cells and tissues under inflammatory conditions. The induction of mPGES-1 in the synovial tissue of RA patients is closely associated with the activation of the tissue by proinflammatory cytokines. Although selective mPGES-1 inhibitors have not yet been widely available, mice lacking mPGES-1 (mPGES-1–/– mice) have been generated to evaluate the physiological and pathological roles of mPGES-1 in vivo. Recent studies utilizing mPGES-1–/– mice have demonstrated the significance of mPGES-1 in the process of chronic inflammation and evocation of humoral immune response in autoimmune arthritis models. These recent findings highlight mPGES-1 as a novel therapeutic target for the treatment of autoimmune inflammatory diseases, including RA. Currently, both natural and synthetic chemicals are being tested for inhibition of mPGES-1 activity to produce PGE2. The present review focuses on the recent advances in understanding the role of mPGES-1 in the pathophysiology of RA.