Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Département de médecine, Faculté de médecine, Université Laval, 2725 Chemin Sainte-Foy, Québec City, QC G1V 4G5, Canada.
Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health, Université Laval, 2325 Rue de l'Université, Québec City, QC G1V 0A6, Canada.
J Leukoc Biol. 2024 May 29;115(6):1183-1189. doi: 10.1093/jleuko/qiae029.
Prostaglandin E2 (PGE2) is a recognized inhibitor of granulocyte functions. However, most of the data supporting this was obtained when available pharmacological tools mainly targeted the EP2 receptor. Herein, we revisited the inhibitory effect of PGE2 on reactive oxygen species production, leukotriene biosynthesis, and migration in human neutrophils. Our data confirm the inhibitory effect of PGE2 on these functions and unravel that the effect of PGE2 on human neutrophils is obtained by the combined action of EP2 and EP4 agonism. Accordingly, we also demonstrate that the inhibitory effect of PGE2 is fully prevented only by the combination of EP2 and EP4 receptor antagonists, underscoring the importance of targeting both receptors in the effect of PGE2. Conversely, we also show that the inhibition of ROS production by human eosinophils only involves the EP4 receptor, despite the fact that they also express the EP2 receptor.
前列腺素 E2（PGE2）是公认的粒细胞功能抑制剂。然而，支持这一观点的大部分数据是在可用的药理学工具主要针对 EP2 受体时获得的。在此，我们重新研究了 PGE2 对人嗜中性粒细胞产生活性氧物质、白三烯生物合成和迁移的抑制作用。我们的数据证实了 PGE2 对这些功能的抑制作用，并揭示了 PGE2 对人嗜中性粒细胞的作用是通过 EP2 和 EP4 激动剂的联合作用获得的。因此，我们还证明，只有 EP2 和 EP4 受体拮抗剂的联合使用才能完全阻止 PGE2 的抑制作用，这凸显了在 PGE2 的作用中靶向这两个受体的重要性。相反，我们还表明，人嗜酸性粒细胞中 ROS 产生的抑制作用仅涉及 EP4 受体，尽管它们也表达 EP2 受体。
