Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, VIC, Australia.
Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, VIC, Australia.
Am J Reprod Immunol. 2018 Apr;79(4):e12825. doi: 10.1111/aji.12825. Epub 2018 Feb 12.
Inflammation plays a major role in preterm birth. Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) plays a role in inflammatory diseases. The aims of this study were to determine the effect of term labor on the expression of NLRP3 in human myometrium and the effect of NLRP3 silencing on pro-labor mediators in myometrial cells.
NLRP3 expression was assessed in myometrium from non-laboring and laboring women by qRT-PCR and Western blotting. Human primary myometrial cells were transfected with NLRP3 siRNA (siNLRP3), treated with pro-inflammatory cytokines and toll-like receptor (TLR) ligands, and assayed for pro-inflammatory mediators' expression.
NLRP3 expression was higher in myometrium after term spontaneous labor and by TNF, IL1B, fsl-1, and flagellin. In siNLRP3-transfected cells, there was a significant decrease in the expression of pro-inflammatory cytokines (IL1A, IL6), chemokines (CXCL8, CCL2), and adhesion molecules (ICAM1 and VCAM1) stimulated with IL1B, TNF, or TLR ligands; decrease in IL1B-stimulated PTGS2 and PTGFR mRNA expression and PGF release; and increase in TNF-stimulated myometrial gel shrinkage as assessed by an in vitro cell contraction assay.
NLRP3 is increased with labor in myometrial, and knockdown of NLRP3 is associated with an attenuation of inflammation-induced expression of pro-inflammatory and pro-labor mediators in human myometrium.
炎症在早产中起主要作用。核苷酸结合寡聚化结构域样受体含吡咯结构域蛋白 3（NLRP3）在炎症性疾病中起作用。本研究旨在确定足月分娩对人子宫肌层 NLRP3 表达的影响，以及 NLRP3 沉默对子宫肌细胞促分娩介质的影响。
通过 qRT-PCR 和 Western blot 评估非分娩和分娩妇女子宫肌层中 NLRP3 的表达。用 NLRP3 siRNA（siNLRP3）转染人原代子宫肌细胞，用促炎细胞因子和 toll 样受体（TLR）配体处理，并检测促炎介质的表达。
足月自发性分娩后和 TNF、IL1B、fsl-1 和 flagellin 刺激后，子宫肌层中 NLRP3 表达增加。在 siNLRP3 转染的细胞中，用 IL1B、TNF 或 TLR 配体刺激后，促炎细胞因子（IL1A、IL6）、趋化因子（CXCL8、CCL2）和粘附分子（ICAM1 和 VCAM1）的表达显著下降；IL1B 刺激的 PTGS2 和 PTGFR mRNA 表达和 PGF 释放减少；TNF 刺激的体外细胞收缩试验评估的子宫肌收缩减少。
NLRP3 在分娩时在子宫肌层中增加，NLRP3 的敲低与炎症诱导的人子宫肌层中促炎和促分娩介质表达的减弱有关。
