Progesterone suppresses the fetal inflammatory response ex vivo
Progesterone suppresses the fetal inflammatory response ex vivo
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DOI：
10.1016/j.ajog.2009.05.012
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发表时间：
2009-08-01
影响因子：
9.8
通讯作者：
Metz, Christine N.
中科院分区：
文献类型：
--
作者：
Schwartz, Nadav;Xue, Xiangying;Metz, Christine N.
目的：补充孕酮已被证明是预防早产的有效方法。本研究旨在探讨孕酮对胎儿炎症反应的影响。研究设计：从脐带血中分离胎儿单个核细胞，在脂多糖(LPS)刺激之前，将胎儿单个核细胞暴露于载药剂或孕酮(P4)1h。测定上清液中肿瘤坏死因子-α的含量。使用环磷酸腺苷(CAMP)和孕酮调节剂也进行了类似的实验。结果：LPS处理后胎儿单个核细胞产生的细胞因子明显增加。尽管缺乏可检测到的NU-Clear孕激素受体，P4抑制了这种炎症反应。孕酮激动剂R5020、cAMP诱导剂Forsklin和cAMP激动剂二丁酰cAMP均有免疫抑制作用。CAMP拮抗剂RP-cAMP可阻断孕酮的抑制作用。结论：孕酮可能通过非基因组激活cAMP级联途径，迅速抑制胎儿炎症反应。
OBJECTIVE: Progesterone supplementation has been shown to be efficacious in preventing preterm birth. We sought to investigate the effects of progesterone on fetal inflammatory responses.STUDY DESIGN: 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.RESULTS: LPS treatment led to a significant increase in cytokine production by fetal mononuclear cells. Despite the lack of detectable nu-clear 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.CONCLUSION: Progesterone rapidly suppresses the fetal inflammatory response, possibly via nongenomic activation of the cAMP cascade.