Inflammatory mediators weaken the amniotic membrane barrier through disruption of tight junctions.
In chorioamnionitis, intra-amniotic infections render the amniotic fluid an adverse environment for the fetus and increase the risk of fetal mortality and morbidity. It remains unclear how infection crosses the amniotic barrier, which is made up of tight junctions (TJs). In this study, we investigated whether amniotic TJs are disrupted in inflammatory conditions such as chorioamnionitis. Amniotic TJs were disrupted by single applications of interleukin (IL)-1β, IL-6, tumour necrosis factor-α (TNF-α), and prostaglandin E2. In organ-cultured amniotic membranes, these inflammatory mediators decreased the claudin-3 and claudin-4 levels at the apical junction at different times. Injecting IL-6 into the amniotic cavity concurrently induced the disruption of amniotic TJs by decreasing the claudin-3 and claudin-4 levels at the apical junction, and the dysfunction of the amniotic barrier; in contrast, injecting TNF-α weakened the amniotic barrier by inducing apoptosis of the amniotic epithelial cells, with no decrease in claudin-3 and claudin-4 at the apical junction. Furthermore, inflammation in the amniotic membrane, which was induced by the administration of lipopolysaccharide to pregnant mice, concurrently caused dysfunction of the amniotic barrier and disruption of TJs, involving the decrease of claudin-3 and claudin-4 levels at the apical junction and apoptosis in the amniotic epithelium. These results indicate that the adverse effects of the inflammatory mediators on amniotic TJs cause severe dysfunction of the amniotic barrier.
Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan. kkobaya@anim.agr.hokudai.ac.jp
Ken
K
Kobayashi
Hideki
H
Miwa
Masato
M
Yasui
D000650:Amnion / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D062465:Claudin-3; D062506:Claudin-4; D016207:Cytokines / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D019108:Tight Junctions / Q000187:drug effects* / Q000502:physiology*
D062465:Claudin-3; D062506:Claudin-4; C568123:Cldn3 protein, mouse; C568158:Cldn4 protein, mouse; D016207:Cytokines; D008070:Lipopolysaccharides; D008565:Membrane Proteins