Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing 400016, China.
Mediators Inflamm. 2020 Jul 11;2020:1069563. doi: 10.1155/2020/1069563. eCollection 2020.
Spontaneous preterm birth (sPTB), defined as delivery before 37 weeks of gestation, is thought to be a multifactorial syndrome. However, the inflammatory imbalance at the maternal-fetal interface promotes excessive secretion of inflammatory factors and induces apoptosis and degradation of the extracellular matrix (ECM), which can subsequently lead to preterm birth. As an anti-inflammatory molecule in the IL-1 family, interleukin-37 (IL-37) mainly plays an inhibiting role in a variety of inflammatory diseases. However, as a typical inflammatory disease, no previous studies have been carried out to explore the role of IL-37 in sPTB. In this study, a series of molecular biological experiments were performed in clinical samples and human amniotic epithelial cell line (Wistar Institute Susan Hayflick (WISH)) to investigate the deficiency role of IL-37 and the potential mechanism. Firstly, the results indicated that the expression of IL-37 in human peripheral plasma and fetal membranes was significantly decreased in the sPTB group. Afterward, it is proved that IL-37 could significantly suppress the production of tumor necrosis factor- (TNF-), interleukin-1 (IL-1), and interleukin-6 (IL-6) in WISH cells. Simultaneously, once silence IL-37, LPS-induced apoptosis and activity of matrix metalloproteinases (MMPs) 2 and 9 were significantly increased. In addition, the western blot data showed that IL-37 performed its biological effects by inhibiting the NF-B and IL-6/STAT3 pathway. In conclusion, our results suggest that IL-37 limits excessive inflammation and subsequently inhibits ECM remodeling and apoptosis through the NF-B and IL-6/STAT3 signaling pathway in the fetal membranes.
自发性早产（sPTB）定义为妊娠 37 周前分娩，被认为是一种多因素综合征。然而，母体-胎儿界面的炎症失衡促进了炎症因子的过度分泌，并诱导了细胞外基质（ECM）的凋亡和降解，随后可能导致早产。白细胞介素-37（IL-37）作为白细胞介素-1 家族中的抗炎分子，主要在各种炎症性疾病中发挥抑制作用。然而，作为一种典型的炎症性疾病，以前没有研究探讨过 IL-37 在 sPTB 中的作用。在这项研究中，在临床样本和人羊膜上皮细胞系（Wistar Institute Susan Hayflick（WISH））中进行了一系列分子生物学实验，以研究 IL-37 的缺乏作用及其潜在机制。首先，研究结果表明，sPTB 组人外周血浆和胎膜中 IL-37 的表达明显降低。随后，证明 IL-37 可显著抑制 WISH 细胞中肿瘤坏死因子-（TNF-）、白细胞介素-1（IL-1）和白细胞介素-6（IL-6）的产生。同时，一旦沉默 IL-37，LPS 诱导的细胞凋亡和基质金属蛋白酶（MMPs）2 和 9 的活性显著增加。此外，Western blot 数据显示，IL-37 通过抑制 NF-B 和 IL-6/STAT3 通路发挥其生物学作用。总之，我们的研究结果表明，IL-37 通过 NF-B 和 IL-6/STAT3 信号通路限制过度炎症，随后抑制 ECM 重塑和凋亡。
