Schwartz Nadav, Xue Xiangying, Elovitz Michal A, Dowling Oonagh, Metz Christine N
Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.
Am J Obstet Gynecol. 2009 Aug;201(2):211.e1-9. doi: 10.1016/j.ajog.2009.05.012.
Progesterone supplementation has been shown to be efficacious in preventing preterm birth. We sought to investigate the effects of progesterone on fetal inflammatory responses.
Fetal mononuclear cells were isolated from umbilical cord blood and exposed to vehicle or progesterone (P4) for 1 hour prior to lipopolysaccharide (LPS) stimulation. Supernatants were assayed for tumor necrosis factor-alpha. Similar experiments were performed using cyclic adenosine monophosphate (cAMP) and progesterone modulators. The effect of P4 treatment on intracellular cAMP levels was also determined.
LPS treatment led to a significant increase in cytokine production by fetal mononuclear cells. Despite the lack of detectable nuclear progesterone receptors, P4 suppressed this inflammatory response. R5020 (progesterone agonist), forskolin (cAMP inducer), and dibutyryl cAMP (cAMP agonist) all achieved immunosuppression. The cAMP antagonist, Rp-cAMP, blocked the inhibitory effect of progesterone. P4 significantly increased intracellular cAMP levels.
Progesterone rapidly suppresses the fetal inflammatory response, possibly via nongenomic activation of the cAMP cascade.
已证明补充孕酮在预防早产方面有效。我们试图研究孕酮对胎儿炎症反应的影响。
从脐带血中分离出胎儿单核细胞，在脂多糖（LPS）刺激前1小时，将其暴露于溶媒或孕酮（P4）中。检测上清液中的肿瘤坏死因子-α。使用环磷酸腺苷（cAMP）和孕酮调节剂进行类似实验。还确定了P4处理对细胞内cAMP水平的影响。
LPS处理导致胎儿单核细胞产生的细胞因子显著增加。尽管未检测到核孕酮受体，但P4抑制了这种炎症反应。R5020（孕酮激动剂）、福斯可林（cAMP诱导剂）和二丁酰cAMP（cAMP激动剂）均实现了免疫抑制。cAMP拮抗剂Rp-cAMP阻断了孕酮的抑制作用。P4显著提高了细胞内cAMP水平。
孕酮可能通过cAMP级联的非基因组激活迅速抑制胎儿炎症反应。
