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

• Published in: Placenta (Eastbourne) Vol. 35; no. 7; pp. 509 - 516
• Main Authors: Tossetta, G, Paolinelli, F, Avellini, C, Salvolini, E, Ciarmela, P, Lorenzi, T, Emanuelli, M, Toti, P, Giuliante, R, Gesuita, R, Crescimanno, C, Voltolini, C, Di Primio, R, Petraglia, F, Castellucci, M, Marzioni, D
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.07.2014; Elsevier
• Subjects: Antigens, CD - genetics; Antigens, CD - metabolism; beta Catenin - genetics; beta Catenin - metabolism; Biological and medical sciences; Cadherins - genetics; Cadherins - metabolism; Case-Control Studies; Cell Membrane Permeability; Chorioamnionitis; Chorioamnionitis - genetics; Chorioamnionitis - pathology; Chorioamnionitis - physiopathology; Cytokines; Cytokines - metabolism; Embryology: invertebrates and vertebrates. Teratology; Female; Fundamental and applied biological sciences. Psychology; Human Umbilical Vein Endothelial Cells; Humans; Immunohistochemistry; Interleukin-1beta - physiology; Internal Medicine; Maternal-Fetal Exchange; Obstetrics and Gynecology; Occludin; Occludin - genetics; Occludin - metabolism; Placenta - physiology; Placenta - physiopathology; Pregnancy; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tight junction; Tight Junctions - pathology; Tight Junctions - physiology; Transforming Growth Factor beta - physiology; Zonula Occludens-1 Protein - genetics; Zonula Occludens-1 Protein - metabolism; Tight junction; Chorioamnionitis; Cytokines; Occludin; In vivo; Vertebrata; Mammalia; Destruction; Placental barrier; Transforming growth factor β; Cytokine; Cell junction; Interleukin 1β; In vitro
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2014.03.016

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.