Murphy Shaun P, Hanna Nazeeh N, Fast Loren D, Shaw Sunil K, Berg Göran, Padbury James F, Romero Roberto, Sharma Surendra
Department of Pediatrics, Women and Infants Hospital of Rhode Island-Warren Alpert Medical School of Brown University, Providence, RI, USA.
Am J Obstet Gynecol. 2009 Mar;200(3):308.e1-9. doi: 10.1016/j.ajog.2008.10.043. Epub 2008 Dec 27.
The purpose of this study was to determine in a mouse model whether uterine natural killer (uNK) cell cytotoxic activation induces infection/inflammation-associated preterm labor and delivery.
Wild type or interleukin (IL)-10(-/-) mice were injected intraperitoneally with lipopolysaccharide on gestational day 14. Mice were either killed for collection of uteroplacental tissue, spleen, and serum or allowed to deliver. Uteroplacental tissue was used for histology and characterization of uNK cells.
Low-dose lipopolysaccharide treatment triggered preterm labor and delivery in IL-10(-/-), but not wild type mice, in a manner independent of progesterone levels. Preterm labor and delivery in IL-10(-/-) mice was associated with an increased number and placental infiltration of cytotoxic uNK cells and placental cell death. Depletion of NK cells or tumor necrosis factor (TNF)-alpha neutralization in these mice restored term delivery. Furthermore, TNF-alpha neutralization prevented uNK cell infiltration and placental cell apoptosis.
The uNK cell-TNF-alpha-IL-10 axis plays an important role in the genesis of infection/inflammation-induced preterm labor/delivery.
本研究旨在通过小鼠模型确定子宫自然杀伤（uNK）细胞的细胞毒性激活是否会引发与感染/炎症相关的早产和分娩。
在妊娠第14天给野生型或白细胞介素（IL）-10基因敲除（-/-）小鼠腹腔注射脂多糖。部分小鼠被处死以收集子宫胎盘组织、脾脏和血清，其余小鼠则任其分娩。子宫胎盘组织用于uNK细胞的组织学检查和特性分析。
低剂量脂多糖处理以一种与孕酮水平无关的方式引发了IL-10（-/-）小鼠而非野生型小鼠的早产和分娩。IL-10（-/-）小鼠的早产和分娩与具有细胞毒性的uNK细胞数量增加、胎盘浸润以及胎盘细胞死亡有关。在这些小鼠中，NK细胞耗竭或肿瘤坏死因子（TNF）-α中和可恢复足月分娩。此外，TNF-α中和可防止uNK细胞浸润和胎盘细胞凋亡。
uNK细胞-TNF-α-IL-10轴在感染/炎症诱导的早产/分娩发生过程中起重要作用。
