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足月自然分娩过程中炎性小体激活的体内证据。

In vivo evidence of inflammasome activation during spontaneous labor at term.

作者信息

Panaitescu Bogdan, Romero Roberto, Gomez-Lopez Nardhy, Xu Yi, Leng Yaozhu, Maymon Eli, Pacora Percy, Erez Offer, Yeo Lami, Hassan Sonia S, Hsu Chaur-Dong

机构信息

a Perinatology Research Branch, NICHD/NIH/DHHS , Detroit , MI , USA.

b Department of Obstetrics & Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.

出版信息

J Matern Fetal Neonatal Med. 2019 Jun;32(12):1978-1991. doi: 10.1080/14767058.2017.1422714. Epub 2018 Jan 17.

Abstract

OBJECTIVE

Upon inflammasome activation, the adaptor protein of the inflammasome ASC (apoptosis-associated speck-like protein containing a CARD) forms intracellular specks, which can be released into the extracellular space. The objectives of this study were to investigate whether (1) extracellular ASC is present in the amniotic fluid of women who delivered at term; (2) amniotic fluid ASC concentrations are greater in women who underwent spontaneous labor at term than in those who delivered at term in the absence of labor; and (3) amniotic epithelial and mesenchymal cells can form intracellular ASC specks in vitro.

METHODS

This retrospective cross-sectional study included amniotic fluid samples from 41 women who delivered at term in the absence of labor (n = 24) or underwent spontaneous labor at term (n = 17). Amniotic epithelial and mesenchymal cells were also isolated from the chorioamniotic membranes obtained from a separate group of women who delivered at term (n = 3), in which ASC speck formation was assessed by confocal microscopy. Monocytes from healthy individuals were used as positive controls for ASC speck formation (n = 3).

RESULTS

(1) The adaptor protein of the inflammasome ASC is detectable in the amniotic fluid of women who delivered at term; (2) amniotic fluid ASC concentration was higher in women who underwent spontaneous labor at term than in those who delivered at term without labor; and (3) amniotic epithelial and mesenchymal cells are capable of forming ASC specks and/or filaments in vitro.

CONCLUSION

Amniotic fluid ASC concentrations are increased in women who undergo spontaneous labor at term. Amniotic epithelial and mesenchymal cells are capable of forming ASC specks, suggesting that these cells are a source of extracellular ASC in the amniotic fluid. These findings provide in vivo evidence that there is inflammasome activation in the amniotic cavity during the physiological process of labor at term.

摘要

目的

在炎性小体激活后,炎性小体ASC(含半胱天冬酶激活和招募结构域的凋亡相关斑点样蛋白)的接头蛋白会形成细胞内斑点,这些斑点可释放到细胞外空间。本研究的目的是调查:(1)足月分娩女性的羊水是否存在细胞外ASC;(2)足月自然分娩女性的羊水ASC浓度是否高于足月未临产分娩女性;(3)羊膜上皮细胞和间充质细胞在体外能否形成细胞内ASC斑点。

方法

这项回顾性横断面研究纳入了41名足月分娩女性的羊水样本,其中未临产者(n = 24)或足月自然分娩者(n = 17)。还从另一组足月分娩女性(n = 3)的绒毛羊膜中分离出羊膜上皮细胞和间充质细胞,通过共聚焦显微镜评估其中ASC斑点的形成情况。将健康个体的单核细胞用作ASC斑点形成的阳性对照(n = 3)。

结果

(1)在足月分娩女性的羊水中可检测到炎性小体ASC的接头蛋白;(2)足月自然分娩女性的羊水ASC浓度高于足月未临产分娩女性;(3)羊膜上皮细胞和间充质细胞在体外能够形成ASC斑点和/或细丝。

结论

足月自然分娩女性的羊水ASC浓度升高。羊膜上皮细胞和间充质细胞能够形成ASC斑点,表明这些细胞是羊水中细胞外ASC的来源。这些发现提供了体内证据,表明足月分娩的生理过程中羊膜腔内存在炎性小体激活。

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