Inflammatory mediators weaken the amniotic membrane barrier through disruption of tight junctions
Inflammatory mediators weaken the amniotic membrane barrier through disruption of tight junctions
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DOI：
10.1113/jphysiol.2010.197764
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发表时间：
2010-12-15
影响因子：
5.5
通讯作者：
Yasui, Masato
中科院分区：
文献类型：
--
作者：
Kobayashi, Ken;Miwa, Hideki;Yasui, Masato
在绒毛膜羊膜炎中，羊膜内感染使羊水成为胎儿的不利环境，并增加胎儿死亡和发病的风险。目前尚不清楚感染是如何穿过羊膜屏障的，羊膜屏障由紧密连接（TJs）组成。在这项研究中，我们调查了羊膜TJs是否在炎症条件下被破坏，如绒毛膜羊膜炎。单次应用白细胞介素(IL)-1 β、IL-6、肿瘤坏死因子- α (tnf - α)和前列腺素E2可破坏羊膜TJs。在器官培养的羊膜中，这些炎症介质在不同时间降低了尖端连接处的claudin-3和claudin-4水平。在羊膜腔内同时注射IL-6，通过降低羊膜顶交界处的claudin-3和claudin-4水平，引起羊膜TJs的破坏，羊膜屏障功能障碍；相反，注射tnf - α通过诱导羊膜上皮细胞凋亡来减弱羊膜屏障，但羊膜上皮细胞顶端交界处的claudin-3和claudin-4的表达没有减少。此外，给孕鼠注射脂多糖引起羊膜炎症，同时引起羊膜屏障功能障碍和TJs破坏，包括羊膜顶端连接处claudin-3和claudin-4水平降低，羊膜上皮细胞凋亡。这些结果表明，炎症介质对羊膜TJs的不良作用导致羊膜屏障严重功能障碍。
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)-1 beta, IL-6, tumour necrosis factor-alpha (TNF-alpha), 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-alpha 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.