Department of Gynecology and Obstetrics, Xiangya Hospital Central South University, Changsha, China.
Department of Physiology, Navy Medical University, Shanghai, China.
Reproduction. 2021 Oct 30;162(6):449-460. doi: 10.1530/REP-21-0047.
The nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays a critical role in various inflammatory diseases. We sought to investigate the role of NLRP3 inflammasome in uterine activation for labor at term and preterm. We found that NLRP3 inflammasome was activated in the myometrium tissues obtained from the pregnant women undergoing labor at term (TL) compared with those not undergoing labor (TNL) at term. NLRP3 inflammasome was also activated in amnion and chorion-deciduas in TL and preterm labor (PTL) groups. In the mouse model, uterine NLRP3 inflammasome and nuclear factor kappaB (NF-κB) were activated toward term and during labor. Treatment of pregnant mice with lipopolysaccharide (LPS) and RU38486 induced preterm birth (PTB) and also promoted uterine NLRP3 inflammasome and NF-κB activation. Treatment of pregnant mice with NLRP3 inflammasome inhibitor BAY11-7082 and MCC950 delayed the onset of labor and suppressed NLRP3 inflammasome and NF-κB activation in uterus. MCC950 postponed labor onset of the mice with LPS and RU38486 treatment and inhibited NLRP3 inflammasome activation in uterus. Our data provide the evidence that NLRP3 inflammasome is involved in uterine activation for labor onset in term and PTB in humans and mouse model.
核苷酸结合寡聚化结构域样受体家族富含吡啶结构域蛋白 3（NLRP3）炎症小体在各种炎症性疾病中发挥着关键作用。我们旨在研究 NLRP3 炎症小体在足月和早产分娩中子宫激活中的作用。我们发现，与足月未分娩（TNL）相比，在足月分娩（TL）孕妇的子宫组织中激活了 NLRP3 炎症小体。在 TL 和早产（PTL）组的羊膜和绒毛-蜕膜中也激活了 NLRP3 炎症小体。在小鼠模型中，子宫 NLRP3 炎症小体和核因子 kappaB（NF-κB）在足月和分娩期间被激活。用脂多糖（LPS）和 RU38486 处理怀孕的小鼠可诱导早产（PTB），并促进子宫 NLRP3 炎症小体和 NF-κB 的激活。用 NLRP3 炎症小体抑制剂 BAY11-7082 和 MCC950 处理怀孕的小鼠可延迟分娩发作，并抑制子宫中的 NLRP3 炎症小体和 NF-κB 激活。MCC950 可推迟 LPS 和 RU38486 处理的小鼠的分娩发作，并抑制子宫中的 NLRP3 炎症小体激活。我们的数据提供了证据，表明 NLRP3 炎症小体参与了人类和小鼠模型中足月和 PTB 分娩的子宫激活。
