Secretory leukocyte protease inhibitor and progranulin as possible regulators of cervical remodeling in pregnancy

• DOI: 10.1016/j.jri.2020.103241
• Publication Date: 2020-11-01T14:39:23Z
• Authors: Taiki Samejima; Takeshi Nagamatsu; Naoya Akiba; Tatsuya Fujii; Seisuke Sayama; Kei Kawana; Ayumi Taguchi; Keiichi Kumasawa; Takayuki Iriyama; Yutaka Osuga; Tomoyuki Fujii
• Keywords: Adult; Lipopolysaccharides; 0301 basic medicine; Cervix Uteri; Up-Regulation; 3. Good health; Disease Models, Animal; Mice; Mifepristone; 03 medical and health sciences; Hormone Antagonists; Progranulins; Pregnancy; Pregnancy Trimester, Second; Models, Animal; Cervix Mucus; Animals; Humans; Premature Birth; Female; Secretory Leukocyte Peptidase Inhibitor; Progesterone; Maternal Age

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.