Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery.

Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery.
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DOI:
10.1016/j.ajog.2008.10.043
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发表时间:
2009-03
影响因子:
9.8
通讯作者:
Sharma, Surendra
Sharma, Surendra
中科院分区:
医学1区
文献类型:
--
作者:
Murphy, Shaun P.;Hanna, Nazeeh N.;Fast, Loren D.;Shaw, Sunil K.;Berg, Goeran;Padbury, James F.;Romero, Roberto;Sharma, Surendra

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这项研究的目的是在小鼠模型中确定子宫自然杀伤(Unk)细胞的细胞毒激活是否会导致感染/炎症相关的早产和分娩。野生型或白介素10(IL-10)−/−小鼠于妊娠第14天腹腔注射脂多糖,处死小鼠采集子宫胎盘组织、脾和血清,或任其分娩。子宫胎盘组织用于Unk细胞的组织学和鉴定。低剂量脂多糖治疗在IL-10−/−小鼠中引发早产和分娩,但不以独立于孕酮水平的方式引发野生型小鼠。IL-10−/−小鼠的早产和分娩与胎盘中细胞毒性Unk细胞的数量增加和胎盘细胞死亡有关。这些小鼠的NK细胞耗尽或肿瘤坏死因子α中和恢复了足月分娩。此外,中和肿瘤坏死因子α可阻止Unk细胞的浸润和胎盘细胞的凋亡。Unk细胞-肿瘤坏死因子-α-IL-10轴在感染/炎症诱导的早产/分娩的发生中起重要作用。
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)α neutralization in these mice restored term delivery. Furthermore, TNFα neutralization prevented uNK cell infiltration and placental cell apoptosis. The uNK cell-TNFα-IL-10 axis plays an important role in the genesis of infection/inflammation-induced preterm labor/delivery.
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