Secretory leukocyte protease inhibitor (SLPI) and progranulin (PGRN) are secretory proteins with an anti-inflammatory property. Their involvement in cervical remodeling in pregnant uterus is not yet elucidated. Thus, this study aimed to explore the significance of SLPI and PGRN in the maintenance of pregnancy by investigating the factors associated with their expression levels at the cervix. Concentrations of SLPI and PGRN proteins were measured in cervical mucus samples collected from asymptomatic pregnant women at 24–26 weeks of gestation (n = 166). The concentrations of those molecules were analyzed with clinical parameters related to risk for preterm delivery (PD). In pregnant mice, we evaluated the effect of lipopolysaccharide-induced inflammation and progesterone effect modulation on cervical mRNA expression of SLPI and PGRN. The cervical PGRN level was significantly lower in women with short cervix (<35 mm) and with a history of threatened PD. In women with short cervix, cervical SLPI concentrations were positively correlated with inflammatory cytokines, interleukin-6 (R² = 0.75) and interleukin-8 (R² = 0.71). In pregnant mice, cervical mRNA expressions of PGRN and SLPI were increased in response to progesterone supplementation and were suppressed by a progesterone antagonist, mifepristone. Lipopolysaccharide-induced inflammation caused remarkable upregulation in cervical SLPI mRNA level but not in PGRN. Progesterone and local inflammation are the factors controlling expression levels of PGRN and SLPI at the cervix. The observed relationship of PGRN and SLPI levels in the cervical mucus with PD-related clinical parameters supports that those anti-inflammatory molecules possibly play a significant role in appropriate regulation of cervical remodeling.

分泌性白细胞蛋白酶抑制剂 (SLPI) 和颗粒蛋白前体 (PGRN) 是具有抗炎特性的分泌性蛋白质。他们在怀孕子宫的宫颈重塑中的参与尚未阐明。因此，本研究旨在通过调查与宫颈表达水平相关的因素来探讨 SLPI 和 PGRN 在维持妊娠中的意义。在从妊娠 24-26 周（n = 166）无症状孕妇收集的宫颈粘液样本中测量 SLPI 和 PGRN 蛋白的浓度。使用与早产 (PD) 风险相关的临床参数分析这些分子的浓度。在怀孕小鼠中，我们评估了脂多糖诱导的炎症和孕酮效应调节对 SLPI 和 PGRN 宫颈 mRNA 表达的影响。宫颈短 (<35 mm) 和有先兆 PD 病史的女性宫颈 PGRN 水平显着降低。在宫颈较短的女性中，宫颈 SLPI 浓度与炎性细胞因子、白细胞介素 6（R² = 0.75) 和白细胞介素 8 (R ² = 0.71)。在怀孕小鼠中，PGRN 和 SLPI 的宫颈 mRNA 表达因补充黄体酮而增加，并被黄体酮拮抗剂米非司酮抑制。脂多糖诱导的炎症导致宫颈 SLPI mRNA 水平显着上调，但在 PGRN 中没有。孕酮和局部炎症是控制宫颈 PGRN 和 SLPI 表达水平的因素。观察到的宫颈粘液中 PGRN 和 SLPI 水平与 PD 相关临床参数的关系支持这些抗炎分子可能在宫颈重塑的适当调节中发挥重要作用。