Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia.
Reproduction. 2019 Jul;158(1):95-107. doi: 10.1530/REP-19-0063.
Inflammation plays a pivotal role in the terminal process of human labor and delivery, including myometrial contractions and membrane rupture. TNF-alpha-induced protein 8-like-2 (TIPE2) is a novel inflammation regulator; however, there are no studies on the role of TIPE2 in human labor. We report that in myometrium, there is decreased TIPE2 mRNA expression during late gestation which was further decreased in labor. In fetal membranes, TIPE2 mRNA expression was decreased with both term and preterm labor compared to no labor samples. Knockdown of TIPE2 by siRNA in primary myometrium and amnion cells was associated with an augmentation of IL1B and TNF-induced expression of pro-inflammatory cytokines and chemokines; expression of contraction-associated proteins and secretion of the uterotonic prostaglandin PGF2α and expression of extracellular matrix degrading enzymes. In TIPE2-deficient myometrial cells treated with inhibitors of NF-κB or ERK1/2, the secretion of pro-labor mediators was reduced back to control levels. In conclusion, these in vitro experiments indicate that loss of TIPE2 exacerbates the inflammatory response.
炎症在人类分娩的终末过程中起着关键作用，包括子宫肌收缩和胎膜破裂。肿瘤坏死因子-α诱导蛋白 8 样蛋白 2（TIPE2）是一种新型的炎症调节剂；然而，目前尚无关于 TIPE2 在人类分娩中的作用的研究。我们报告说，在子宫肌中，TIPE2mRNA 的表达在妊娠晚期下降，在分娩时进一步下降。与无分娩样本相比，足月和早产胎膜中 TIPE2mRNA 的表达也下降。用 siRNA 在原代子宫肌和羊膜细胞中敲低 TIPE2，与促炎细胞因子和趋化因子的表达增加有关；与收缩相关的蛋白的表达和促子宫收缩的前列腺素 PGF2α 的分泌以及细胞外基质降解酶的表达有关。在 NF-κB 或 ERK1/2 抑制剂处理的 TIPE2 缺陷型子宫肌细胞中，促分娩介质的分泌减少到对照水平。总之，这些体外实验表明，TIPE2 的缺失加剧了炎症反应。
