Lewis G D, Campbell W B, Johnson A R
Endocrinology. 1986 Jul;119(1):62-9. doi: 10.1210/endo-119-1-62.
The vasodilator prostaglandins (PGs), prostacyclin (PGI2) and PGE2, may contribute to the inflammatory response. Because glucocorticosteroids reduce inflammation, possibly through inhibition of arachidonic acid release, we examined the influence of dexamethasone on PG formation in cultures of human endothelial cells. Binding of [3H]dexamethasone by intact cells was competed by unlabeled steroids and was half-maximal at 1.2 X 10(-8) M. A cytosolic fraction complexed with [3H]dexamethasone and migrated on sucrose density gradient centrifugation with a sedimentation coefficient of 8S. 3H-steroid binding was diminished by unlabeled steroid. Histamine, bradykinin, and the ionophore, A23187, stimulated release of PGI2 and PGE2 to as much as 25 times basal release. Dexamethasone (10(-11) to 10(-7) M) reduced PG formation in cells that were stimulated by histamine, bradykinin, calcium ionophore, or mechanical agitation. The inhibitory effect required at least 4 h to develop, was maximal at 24 h, and persisted after the steroid was removed. Hydrocortisone and triamcinolone had similar effects but were less potent than dexamethasone. Testosterone and progesterone did not affect PG generation. Both arachidonic acid and PGH2 augmented formation of PGs but were not inhibited by dexamethasone. Cortisol-21-mesylate, an antagonist of glucocorticoid receptors, blocked the effects of dexamethasone on PG formation, as did treatment of the cells with cycloheximide. We conclude that glucocorticoids inhibit PG production in endothelial cells by interaction with specific steroid receptors. The steroid-mediated inhibitory effect occurs at the level of arachidonic acid release and depends upon protein synthesis.
血管扩张性前列腺素（PGs）、前列环素（PGI2）和前列腺素E2（PGE2）可能参与炎症反应。由于糖皮质激素可能通过抑制花生四烯酸释放来减轻炎症，我们研究了地塞米松对人内皮细胞培养物中PG生成的影响。完整细胞对[3H]地塞米松的结合可被未标记的类固醇竞争，半数最大结合浓度为1.2×10^(-8)M。一种与[3H]地塞米松结合的胞质组分在蔗糖密度梯度离心中迁移，沉降系数为8S。未标记的类固醇可减少3H-类固醇结合。组胺、缓激肽和离子载体A23187可刺激PGI2和PGE2的释放，使其高达基础释放量的25倍。地塞米松（10^(-11)至10^(-7)M）可减少组胺、缓激肽、钙离子载体或机械搅拌刺激的细胞中的PG生成。这种抑制作用至少需要4小时才能显现，在24小时时达到最大，并在去除类固醇后持续存在。氢化可的松和曲安西龙有类似作用，但效力低于地塞米松。睾酮和孕酮不影响PG生成。花生四烯酸和PGH2均可增加PG生成，但不受地塞米松抑制。糖皮质激素受体拮抗剂甲磺酸皮质醇-21可阻断地塞米松对PG生成的作用，用环己酰亚胺处理细胞也有同样效果。我们得出结论，糖皮质激素通过与特定类固醇受体相互作用抑制内皮细胞中的PG产生。类固醇介导的抑制作用发生在花生四烯酸释放水平，且依赖于蛋白质合成。
