Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University.
Biol Pharm Bull. 2022;45(8):979-984. doi: 10.1248/bpb.b22-00370.
Prostacyclin (PGI) synthase (PGIS) and microsomal prostaglandin (PG) E synthase-1 (PGES-1) are PG terminal synthases which functionally couple with inducible cyclooxygenase-2 (COX-2) as their upstream enzymes to produce PGI and PGE, respectively. Non-steroidal anti-inflammatory drugs exert their pharmacological effects by the inhibition of COX-2 and thereby suppression of the biosynthesis of these PGs. PGIS is abundantly expressed in vascular endothelial and smooth muscle cells and has been shown to be critical for regulation of platelet aggregation and vascular tone. In addition to its role in vascular regulation, PGIS has been shown to be expressed in inflammatory cells including macrophages, and the proinflammatory roles of PGIS has been demonstrated. On the other hand, several investigators have recently reported that PGIS functions as an anti-inflammatory mediator by macrophage polarization and have indicated that PGIS is an ambivalent regulator of inflammatory reactions. In this review, we summarize the current understanding of proinflammatory and anti-inflammatory functions of PGIS and discuss its potential as a novel anti-inflammatory therapeutic target.
前列环素（PGI）合酶（PGIS）和微粒体前列腺素（PG）E 合酶-1（PGES-1）是 PG 末端合酶，它们与诱导型环氧化酶-2（COX-2）作为其上游酶功能性偶联，分别产生 PGI 和 PGE。非甾体抗炎药通过抑制 COX-2 发挥其药理作用，从而抑制这些 PG 的生物合成。PGIS 在血管内皮细胞和平滑肌细胞中大量表达，对于调节血小板聚集和血管张力至关重要。除了在血管调节中的作用外，PGIS 还被证明在包括巨噬细胞在内的炎症细胞中表达，并且已经证明了 PGIS 的促炎作用。另一方面，最近一些研究人员报告称，PGIS 通过巨噬细胞极化发挥抗炎介质的作用，并指出 PGIS 是炎症反应的双重调节因子。在这篇综述中，我们总结了 PGIS 的促炎和抗炎功能的最新认识，并讨论了它作为一种新型抗炎治疗靶点的潜力。
