Hanna Nazeeh, Bonifacio Lea, Reddy Pradeep, Hanna Iman, Weinberger Barry, Murphy Shaun, Laskin Debra, Sharma Surendra
Division of Neonatology, Department of Pediatrics, UMDNJ-Robert Wood, Johnson Medical School, New Brunswick, NJ 08903, USA.
Am J Reprod Immunol. 2004 Apr;51(4):311-8. doi: 10.1111/j.1600-0897.2004.00162.x.
The inflammatory-anti-inflammatory cytokine network is thought to play a critical role in regulated progression and termination of pregnancy. The aim of this study was to evaluate the effects of interferon (IFN)-gamma on the expression of Cyclooxygenase (COX)-2 and production of prostaglandin E(2) (PGE(2)) in the human placenta from term and preterm labor deliveries.
Placental explant culture system was used. COX-2 expression was determined by complementary techniques of immunohistochemistry and Western blotting. Released IFN-gamma and PGE(2) by placental explants were measured by enzyme-linked immunosorbent assay. Signal transducer and activator of transcription 1 (STAT1) phosphorylation was evaluated by Western blotting using a specific antibody.
IFN-gamma was poorly detected in the placenta but was significantly expressed in decidual tissues from both term and preterm pregnancies as detected by immunohistochemistry. IFN-gamma significantly inhibited COX-2 expression and PGE(2) release in cultured placental explants from term and preterm labor deliveries. This effect most likely occurred in a STAT1-dependent manner as this regulatory protein was phosphorylated in response to IFN-gamma. IFN-gamma receptor (IFN-gammaR) was expressed in normal early pregnancy placental samples. However, its expression was significantly reduced in placental samples from term and preterm deliveries. Of interest, IFN-gammaR was expressed in placentas from term and preterm labor deliveries after 24 hr in culture.
Our data suggest that the human placenta is an important site for IFN-gamma-mediated repression of COX-2 expression and PGE2 production, implying that functional withdrawal of IFN-gamma may be involved in the onset of term or preterm labor.
炎症-抗炎细胞因子网络被认为在妊娠的调节进展和终止中起关键作用。本研究的目的是评估干扰素（IFN）-γ对足月和早产分娩的人胎盘中环氧化酶（COX）-2表达及前列腺素E2（PGE2）产生的影响。
采用胎盘外植体培养系统。通过免疫组织化学和蛋白质印迹的互补技术测定COX-2表达。采用酶联免疫吸附测定法测量胎盘外植体释放的IFN-γ和PGE2。使用特异性抗体通过蛋白质印迹评估信号转导和转录激活因子1（STAT1）的磷酸化。
通过免疫组织化学检测发现，IFN-γ在胎盘中检测不到，但在足月和早产妊娠的蜕膜组织中均有显著表达。IFN-γ显著抑制足月和早产分娩的培养胎盘外植体中COX-2的表达和PGE2的释放。这种作用很可能以STAT1依赖的方式发生，因为这种调节蛋白在IFN-γ作用下发生了磷酸化。IFN-γ受体（IFN-γR）在正常早孕胎盘样本中表达。然而，其在足月和早产胎盘样本中的表达显著降低。有趣的是，培养24小时后，足月和早产分娩的胎盘中均表达IFN-γR。
我们的数据表明，人胎盘是IFN-γ介导抑制COX-2表达和PGE2产生的重要部位，这意味着IFN-γ功能的丧失可能与足月或早产的发动有关。
