IL-1β and TGF-β weaken the placental barrier through destruction of tight junctions: an in vivo and in vitro study

Abstract

Introduction: Chorioamnionitis is a gestational pathological condition characterized by acute inflammation of the amniochorionic membranes and placentas leading to high concentrations of IL-1β, Il-6, Il-8 and TGF-β in the amniotic fluid. In normal conditions, the permeability of foeto-maternal barrier is due to the assembly and maintenance of different cellular junctional domains.

Methods: In the present study, first we aimed to evaluate the protein expression (by immunohistochemistry and western blotting) and mRNA (by real time PCR) levels of the molecular components of tight junctions (Zonula occludens-1 and occludin), and of adherent junctions (VE-cadherin and β-catenin) in placentas from chorioamnionitis compared to that in normal pregnancies.

Results: Western blotting results showed a significant down-regulation of occludin in placentas affected with chorioamnionitis. No differences were detected for the other proteins analysed. We evaluated whether occludin expression was regulated by IL-1β, IL-6, IL-8 and TGF-β by means of in vitro studies using HUVEC cultures and demonstrated a key role of IL-1β and TGF-β in the disappearance of occludin at cellular border.

Conclusions: We conclude by suggesting a pivotal role of these two cytokines in facilitating intra-placental infection via para-cellular way due to the disassembly of tight junctions at trophoblastic and endothelial cells in placental tissues.

Keywords: Chorioamnionitis; Cytokines; Occludin; Tight junction.