Mirazi Nasser, Alfaidy Nadia, Martin Rebecca, Challis John R G
Canadian Institutes for Health Research, Group in Fetal and Neonatal Health and Development, University of Toronto, Toronto, Ontario, Canada.
J Soc Gynecol Investig. 2004 Jan;11(1):22-6. doi: 10.1016/j.jsgi.2003.07.005.
Prostaglandins (PG) are key mediators of the labor process. We investigated effects of dexamethasone on PGE2 output in term human placental cells in the presence of indomethacin, an inhibitor of PGH synthase enzymes PGHS1 and PGHS2 activity; meloxicam, a relatively specific inhibitor of PGHS2; and sulfasalazine, an inhibitor of 15-OH PG dehydrogenase (PGDH), a PG-metabolizing enzyme.
Cells were treated for 24 hours with indomethacin (1 microM), meloxicam (1 microM), sulfasalazine (1 microM), or combinations of these three compounds in the presence or absence of glucocorticoids.
Meloxicam alone had no effect on basal output of PGE2. Dexamethasone produced a significant, almost doubling of PGE2 output, but this was not altered further by meloxicam. Sulfasalazine alone doubled the output of PGE2, and this increased further in the presence of dexamethasone. That increase was reduced by addition of meloxicam. Indomethacin significantly reduced stimulation of PGE2 output measured after dexamethasone treatment. In addition, indomethacin significantly attenuated the stimulation of PGE2 output seen with the addition of sulfasalazine or the further increase seen with sulfasalazine plus dexamethasone.
Basal PGE2 output by placental cells likely depends on the activity of PGHS1, not PGHS2. The effects of sulfasalazine suggest the importance of endogenous PGDH in regulating PGE2 output, and interactions with sulfasalazine, dexamethasone, and meloxicam suggest that glucocorticoid-stimulated output of PGE2 by placental cells may be attributable to both up-regulation of PGHS and down-regulation of PGDH.
前列腺素（PG）是分娩过程的关键介质。我们研究了地塞米松在吲哚美辛（一种PGH合酶PGHS1和PGHS2活性抑制剂）、美洛昔康（一种相对特异性的PGHS2抑制剂）和柳氮磺胺吡啶（一种PG代谢酶15-羟基PG脱氢酶（PGDH）的抑制剂）存在的情况下对足月人胎盘细胞中PGE2产量的影响。
在有或没有糖皮质激素的情况下，用吲哚美辛（1微摩尔）、美洛昔康（1微摩尔）、柳氮磺胺吡啶（1微摩尔）或这三种化合物的组合处理细胞24小时。
单独使用美洛昔康对PGE2的基础产量没有影响。地塞米松使PGE2产量显著增加，几乎增加了一倍，但美洛昔康对此没有进一步改变。单独使用柳氮磺胺吡啶使PGE2产量增加了一倍，在地塞米松存在的情况下进一步增加。加入美洛昔康后，这种增加有所减少。吲哚美辛显著降低了地塞米松处理后测得的PGE2产量刺激。此外，吲哚美辛显著减弱了添加柳氮磺胺吡啶时观察到的PGE2产量刺激或柳氮磺胺吡啶加地塞米松时观察到的进一步增加。
胎盘细胞的基础PGE2产量可能取决于PGHS1的活性，而不是PGHS2。柳氮磺胺吡啶的作用表明内源性PGDH在调节PGE2产量中的重要性，并且与柳氮磺胺吡啶、地塞米松和美洛昔康的相互作用表明糖皮质激素刺激的胎盘细胞PGE2产量可能归因于PGHS的上调和PGDH的下调。
