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Updated: Oct 15, 2025

A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
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IL-27 Mediates Pro-Inflammatory Effects via the ERK Signaling Pathway During Preterm Labor

Dongni Huang1,2,3, Yuxin Ran1,2,3, Zheng Liu1,2,3

  • 1Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Frontiers in Immunology
|October 25, 2021
PubMed

Insights

Interleukin-27 (IL-27) signaling via the WSX-1 receptor promotes preterm labor (PTL) by increasing inflammatory markers. Inhibiting the ERK pathway reduces these pro-inflammatory effects, offering new insights into PTL mechanisms.

Area of Science:

  • Reproductive Biology
  • Immunology
  • Molecular Mechanisms

Background:

  • Preterm labor (PTL) is a leading cause of neonatal morbidity and mortality.
  • The precise molecular pathways driving PTL remain incompletely understood.
  • Previous studies suggest a role for Interleukin-27 (IL-27) in PTL pathophysiology.

Purpose of the Study:

  • To investigate the role of the IL-27 receptor WSX-1 in an infection-induced preterm labor mouse model.
  • To elucidate the downstream inflammatory mediators and signaling pathways involved in IL-27-driven PTL.
  • To assess the therapeutic potential of targeting the IL-27 pathway in PTL.

Main Methods:

  • Established a Lipopolysaccharide (LPS)-stimulated, infection-induced preterm mouse model using wild-type and WSX-1 knockout mice.
  • Quantified the expression of key inflammatory cytokines (IFN-γ, IL-1β, IL-6, TNF-α, CXCL10) in maternal and fetal tissues.
  • Utilized human amniotic (WISH) and myometrial (HMSMC) cell lines to confirm IL-27's pro-inflammatory effects and tested the efficacy of an ERK pathway inhibitor (LY3214996).

Main Results:

  • WSX-1 deficiency significantly delayed birth in the preterm mouse model.
  • Knockdown of WSX-1 led to markedly reduced expression of inflammatory cytokines in the fetal membrane and myometrium.
  • IL-27 induced synergistic and time-dependent pro-inflammatory responses in human cells, which were attenuated by LY3214996, indicating ERK pathway involvement.

Conclusions:

  • The IL-27/WSX-1 axis plays a critical role in mediating inflammation associated with preterm labor.
  • Inflammatory mediators such as IFN-γ, IL-1β, IL-6, TNF-α, and CXCL10 are key downstream effectors.
  • Targeting the IL-27/IFN-γ/ERK signaling pathway presents a potential therapeutic strategy for preventing PTL.

Keywords:
ERK signaling pathwayIL-27/WSX-1inflammationmice modelpreterm labor

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