Fortunato S J, Menon R
The Perinatal Research Center of The Women's Health Research and Education Foundation and Aquinas College, 2300 Patterson Street, Nashville, TN 37203, USA.
Placenta. 2003 Nov;24(10):922-8. doi: 10.1016/s0143-4004(03)00160-7.
The objective of this study was to compare two of the inflammatory cytokines (IL-1 and IL-6) elevated in both preterm labour and preterm premature rupture of the membranes (pPROM), with respect to their ability to induce fetal membrane apoptosis. Fetal membranes collected from women at term were placed in an organ explant system and stimulated with recombinant human IL-1 beta and IL-6. The expression patterns of pro-apoptotic genes (Fas, FasL, TRADD, FADD) and caspases 2, 3, 8, 9 were studied using PCR. Caspase activity and DNA fragmentation were studied using substrate assays and TUNEL respectively. Caspase 8 and 9 expressions were induced in IL-1 beta and IL-6 treated amniochorion. Caspase 2 expression was seen only in IL-1 beta stimulated tissues. When compared to control, IL-1 beta increased caspase 2, 3, 8 and 9 activities, whereas IL-6 treated membranes did not exhibit a significant change. DNA fragmentation was seen in greater numbers after IL-1 beta treatment than after IL-6 treatment. This study demonstrates that IL-1 beta is a better inducer of apoptosis in normal human fetal membranes than IL-6.
本研究的目的是比较两种在早产和胎膜早破（pPROM）中均升高的炎性细胞因子（IL-1和IL-6）诱导胎膜凋亡的能力。从足月孕妇收集的胎膜置于器官外植体系统中，并用重组人IL-1β和IL-6进行刺激。使用PCR研究促凋亡基因（Fas、FasL、TRADD、FADD）以及半胱天冬酶2、3、8、9的表达模式。分别使用底物分析和TUNEL研究半胱天冬酶活性和DNA片段化。在IL-1β和IL-6处理的羊膜绒毛膜中诱导了半胱天冬酶8和9的表达。仅在IL-1β刺激的组织中观察到半胱天冬酶2的表达。与对照相比，IL-1β增加了半胱天冬酶2、3、8和9的活性，而IL-6处理的胎膜未表现出显著变化。与IL-6处理后相比，IL-1β处理后观察到更多的DNA片段化。本研究表明，在正常人胎膜中，IL-1β比IL-6是更好的凋亡诱导剂。
