Westover Alana, Melville Jacqueline M, McDonald Courtney, Lim Rebecca, Jenkin Graham, Wallace Euan M, Moss Timothy J
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia.
Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia.
Front Physiol. 2017 Nov 6;8:871. doi: 10.3389/fphys.2017.00871. eCollection 2017.
Intra-amniotic (IA) lipopolysaccharide (LPS) injection in sheep induces inflammation in the fetus. Human amnion epithelial cells (hAECs) moderate the effect of IA LPS on fetal development, but their influence on the acute inflammatory response to IA LPS is unknown. We aimed to determine the effects of hAECs on the acute fetal inflammatory response to IA LPS. After surgical instrumentation at 116 days' gestation (d) ewes were randomized to 1 of 4 groups at 123 d: IA LPS (10 mg) and intravenous (IV) saline ( = 8), IA LPS and IV hAECs ( = 6), IA saline and IV saline ( = 5) or IA saline and IV hAECs ( = 5). IV injections were administered immediately after IA injections. Serial fetal blood samples were collected. At 125 d, placental, fetal lung and liver samples were collected. IA LPS increased inflammatory cell recruitment in the placenta and lungs, increased IL-1β and IL-8 mRNA levels in the lungs and increased serum amyloid A3 (SAA3) and C-reactive protein (CRP) mRNA levels in the liver. IV hAECs reduced fetal lung inflammatory cell recruitment but did not otherwise alter indices of placental, fetal lung or liver inflammation. The acute fetal inflammatory response to IA LPS is not substantially altered by IV hAEC treatment.
在绵羊羊膜腔内注射脂多糖(LPS)可诱发胎儿炎症。人羊膜上皮细胞(hAECs)可减轻羊膜腔内LPS对胎儿发育的影响,但其对羊膜腔内LPS急性炎症反应的影响尚不清楚。我们旨在确定hAECs对羊膜腔内LPS急性胎儿炎症反应的影响。在妊娠116天(d)进行手术操作后,母羊在123 d被随机分为4组中的1组:羊膜腔内注射LPS(10 mg)并静脉注射生理盐水(n = 8),羊膜腔内注射LPS并静脉注射hAECs(n = 6),羊膜腔内注射生理盐水并静脉注射生理盐水(n = 5)或羊膜腔内注射生理盐水并静脉注射hAECs(n = 5)。在羊膜腔内注射后立即进行静脉注射。采集系列胎儿血样。在125 d时,采集胎盘、胎儿肺和肝脏样本。羊膜腔内注射LPS增加了胎盘和肺中炎症细胞的募集,增加了肺中白细胞介素-1β(IL-1β)和白细胞介素-8(IL-8)的mRNA水平,并增加了肝脏中血清淀粉样蛋白A3(SAA3)和C反应蛋白(CRP)的mRNA水平。静脉注射hAECs减少了胎儿肺炎症细胞的募集,但未改变胎盘、胎儿肺或肝脏炎症的其他指标。静脉注射hAECs治疗并未显著改变对羊膜腔内LPS的急性胎儿炎症反应。