Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of MelbourneMelbourne, Victoria, Australia.
Mercy Perinatal Research CentreMercy Hospital for Women, Heidelberg, Victoria, Australia.
Reproduction. 2018 Feb;155(2):207-218. doi: 10.1530/REP-17-0604.
Preterm birth is a prevalent cause of neonatal deaths worldwide. Inflammation has been implicated in spontaneous preterm birth involved in the processes of uterine contractility and membrane rupture. Parkinson protein 7 (PARK7) has been found to play an inflammatory role in non-gestational tissues. The aims of this study were to determine the expression of PARK7 in myometrium and fetal membranes with respect to term labour onset and to elucidate the effect of PARK7 silencing in primary myometrium and amnion cells on pro-inflammatory and pro-labour mediators. mRNA expression was higher in term myometrium and fetal membranes from women in labour compared to non-labouring samples and in amnion from preterm deliveries with chorioamnionitis. In human primary myometrial cells transfected with PARK7 siRNA (siPARK7), there was a significant decrease in IL1B, TNF, fsl-1 and poly(I:C)-induced expression of pro-inflammatory cytokine IL6, chemokines (CXCL8, CCL2), adhesion molecule ICAM1, prostaglandin PGF and its receptor PTGFR. Similarly, amnion cells transfected with siPARK7 displayed a decrease in IL1B-induced expression of IL6, CXCL8 and ICAM1. In myometrial cells transfected with siPARK7, there was a significant reduction of NF-κB RELA transcriptional activity when stimulated with fsl-1, flagellin and poly(I:C), but not with IL1B or TNF. Collectively, our novel data describe a role for PARK7 in regulating inflammation-induced pro-inflammatory and pro-labour mediators in human myometrial and amnion cells.
早产是全球新生儿死亡的一个主要原因。炎症在自发性早产中起作用，涉及子宫收缩和膜破裂的过程。Parkinson 蛋白 7 (PARK7) 已被发现在非妊娠组织中发挥炎症作用。本研究旨在确定 PARK7 在足月分娩和早产伴绒毛膜羊膜炎的肌层和胎膜中的表达，并阐明 PARK7 沉默对原代肌层和羊膜细胞促炎和促分娩介质的影响。与非分娩样本相比，分娩时足月肌层和胎膜以及早产伴绒毛膜羊膜炎的胎膜中 PARK7 mRNA 的表达更高。在转染 PARK7 siRNA (siPARK7) 的人原代肌层细胞中，IL1B、TNF、fsl-1 和 poly(I:C) 诱导的促炎细胞因子 IL6、趋化因子 (CXCL8、CCL2)、粘附分子 ICAM1、前列腺素 PGF 和其受体 PTGFR 的表达显著降低。同样，转染 siPARK7 的羊膜细胞中，IL1B 诱导的 IL6、CXCL8 和 ICAM1 的表达也减少。在转染 siPARK7 的肌层细胞中，fsl-1、鞭毛蛋白和 poly(I:C)刺激时 NF-κB RELA 转录活性显著降低，但 IL1B 或 TNF 刺激时则没有。总之，我们的新数据描述了 PARK7 在调节人肌层和羊膜细胞中炎症诱导的促炎和促分娩介质中的作用。
