IL-1β stimulates ADAMTS9 expression and contributes to preterm prelabor rupture of membranes

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 8, 2025

Preterm prelabor rupture of membranes (pPROM) is a leading cause neonatal morbidity and mortality. While intra-amniotic infection well-established driver pPROM, the role sterile inflammation remains unclear. Recent evidence suggests that interleukin-1 beta (IL-1β) promotes extracellular matrix (ECM) remodeling via downstream effectors, disintegrin-like metalloproteinase domain with thrombospondin type 1 motif 9 (ADAMTS9), while protein O-fucosyltransferase 2 (POFUT2) facilitates its O-fucosylation secretion, amplifying ECM degradation. This study investigates how IL-1β-triggered nuclear factor kappa-B (NF-κB) activation ADAMTS9 POFUT2 expression, ultimately driving fetal membrane weakening in pPROM without signs infection. A nested case-control included maternal serum samples from 60 pregnant women (34 26 full-term births [FTB]). ELISA measured levels IL-1β ADAMTS9, their correlations were analyzed. Mechanistic studies utilized primary human amniotic epithelial cells (hAECs) membrane-decidua explants treatment. The NF-κB was explored using chromatin immunoprecipitation (ChIP) luciferase assays to assess binding promoters POFUT2. murine model under ultrasound-guided injection used validate vitro findings pregnancy outcomes. Serum at 16 weeks gestation significantly higher cases compared FTB controls (P < 0.001). combined these biomarkers demonstrated high predictive accuracy for (AUC = 0.83). Mechanistically, activated NF-κB, promoted enhanced secretion. Together, processes drove versican degradation weakening. Intra-amniotic administration mice induced weakening, preterm birth, adverse outcomes, which mitigated by inhibitor BAY 11-7082 Maternal mid-gestation are promising non-invasive risk stratification. IL-1β-induced expression POFUT2-dependent contributing These provide new insights into potential therapeutic target pPROM.

Language: Английский

Host-microbiome interactions in distinct subsets of preterm labor and birth

iScience, Journal Year: 2023, Volume and Issue: 26(12), P. 108341 - 108341

Published: Oct. 28, 2023

Preterm birth, the leading cause of perinatal morbidity, often follows premature labor, a syndrome whose prevention remains challenge. To better understand relationship between labor and host-microbiome interactions, we conducted mechanistic investigation using three preterm birth models. We report that intra-amniotic delivery LPS triggers inflammatory responses in amniotic cavity cervico-vaginal microenvironment, causing vaginal microbiome changes signs active labor. Intra-amniotic IL-1α causes moderate response but increasing inflammation space, to disruption Conversely, progesterone action blockade by RU-486 local immune accompanying without altering microbiome. facilitates ascension bacteria into cavity, regardless stimulus. This study provides compelling insights dynamic interactions within microenvironment accompany birth.

Language: Английский

Distinct maternofetal immune signatures delineate preterm birth onset following urinary tract infection

Published: Oct. 25, 2024

ABSTRACT Preterm birth is the leading cause of infant mortality resulting in over one million neonatal deaths annually. Maternal urinary tract infection (UTI) during pregnancy increases risk for preterm birth; however, biological processes mediating UTI-associated are not well-described. We established a murine maternal UTI model which challenge with uropathogenic E. coli resulted about half dams. Dams experiencing displayed excessive bladder inflammation and altered uteroplacental T cell polarization compared to non-laboring infected dams, no differences bacterial burdens. Additional factors associated included higher proportions male fetuses lower serum IL-10. Furthermore, exogenous IL-10 treatment absolved but contributed fetal growth restriction this model. Using urine samples from cohort human pregnancies or without UTI, we correlated cytokines outcomes culture status. These analyses yielded non-invasive, highly predictive three-model system evaluating implicating IL-10, IL-15, IL-1β, IL-1RA. Our unique bimodal coupled patient provides platform investigate immunological microbial governing birth, revealing novel therapeutic opportunities predict prevent birth.

Language: Английский