Ovine fetal thymus response to lipopolysaccharide-induced chorioamnionitis and antenatal corticosteroids.
Ovine fetal thymus response to lipopolysaccharide-induced chorioamnionitis and antenatal corticosteroids.
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DOI：
10.1371/journal.pone.0038257
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kramer BW
中科院分区：
文献类型：
--
作者：
Kuypers E;Collins JJ;Jellema RK;Wolfs TG;Kemp MW;Nitsos I;Pillow JJ;Polglase GR;Newnham JP;Germeraad WT;Kallapur SG;Jobe AH;Kramer BW
绒毛膜羊膜炎与早产和胎儿胸腺退化有关。有早产风险的妇女在产前接受皮质类固醇治疗，这会加速胎儿肺成熟，改善新生儿结局。然而，在绒毛膜羊膜炎的情况下，产前皮质类固醇对胎儿胸腺的影响在很大程度上是未知的。我们假设羊膜腔内暴露于脂多糖(LPS)会导致胎儿胸腺退缩，从而对胸腺结构和细胞群产生持续的影响。我们还假设，产前皮质类固醇可能调节内毒素对胸腺发育的影响。时间交配的单胎母羊在胎龄120d(足月 = 150d)早产前7天或14天羊膜内注射脂多糖。脂多糖和皮质类固醇治疗组在母体肌肉注射倍他米松之前或之后接受羊膜腔内脂多糖治疗。与妊娠相匹配的对照组接受羊水和母体肌肉注射生理盐水。对胎儿胸腺进行评价。羊膜腔内注射脂多糖可降低胸腺皮质髓质(C/M)比值，增加Toll样受体(TLR4mRNA)和CD3的表达，提示胎儿胸腺退化和活化。TLR4和CD3表达增加持续14天，而Foxp3表达下降，提示调节性T细胞发生改变。Sonic Hedgehog和骨形态发生蛋白4mRNA是T细胞发育的负调控因子，在羊膜腔内脂多糖的作用下，它们的表达下降。内毒素暴露前倍他米松处理可减弱部分内毒素诱导的胸腺反应，但增加caspase-3的裂解表达，降低C/M比值。内毒素暴露后，倍他米松治疗不能阻止内毒素引起的胸腺改变。羊膜腔内暴露于脂多糖可激活胎儿胸腺，并伴有结构改变。产前给予糖皮质激素治疗可部分减弱脂多糖诱导的效应，但增加胎儿胸腺的细胞凋亡。炎症刺激后给予糖皮质激素并不能抑制内毒素对胎儿胸腺的作用。
Chorioamnionitis is associated with preterm delivery and involution of the fetal thymus. Women at risk of preterm delivery receive antenatal corticosteroids which accelerate fetal lung maturation and improve neonatal outcome. However, the effects of antenatal corticosteroids on the fetal thymus in the settings of chorioamnionitis are largely unknown. We hypothesized that intra-amniotic exposure to lipopolysaccharide (LPS) causes involution of the fetal thymus resulting in persistent effects on thymic structure and cell populations. We also hypothesized that antenatal corticosteroids may modulate the effects of LPS on thymic development. Time-mated ewes with singleton fetuses received an intra-amniotic injection of LPS 7 or 14 days before preterm delivery at 120 days gestational age (term = 150 days). LPS and corticosteroid treatment groups received intra-amniotic LPS either preceding or following maternal intra-muscular betamethasone. Gestation matched controls received intra-amniotic and maternal intra-muscular saline. The fetal intra-thoracic thymus was evaluated. Intra-amniotic LPS decreased the cortico-medullary (C/M) ratio of the thymus and increased Toll-like receptor (TLR) 4 mRNA and CD3 expression indicating involution and activation of the fetal thymus. Increased TLR4 and CD3 expression persisted for 14 days but Foxp3 expression decreased suggesting a change in regulatory T-cells. Sonic hedgehog and bone morphogenetic protein 4 mRNA, which are negative regulators of T-cell development, decreased in response to intra-amniotic LPS. Betamethasone treatment before LPS exposure attenuated some of the LPS-induced thymic responses but increased cleaved caspase-3 expression and decreased the C/M ratio. Betamethasone treatment after LPS exposure did not prevent the LPS-induced thymic changes. Intra-amniotic exposure to LPS activated the fetal thymus which was accompanied by structural changes. Treatment with antenatal corticosteroids before LPS partially attenuated the LPS-induced effects but increased apoptosis in the fetal thymus. Corticosteroid administration after the inflammatory stimulus did not inhibit the LPS effects on the fetal thymus.
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影响因子：
3.8
作者：
Hanson ML;Brundage KM;Schafer R;Tou JC;Barnett JB
通讯作者：
Barnett JB
影响因子：
3.3
作者：
Bakker, JM;Schmidt, ED;vanRees, EP
通讯作者：
vanRees, EP
DOI：
10.1152/ajplung.2001.280.3.l527
发表时间：
2001-03-01
影响因子：
4.9
作者：
Kallapur, SG;Willet, KE;Bachurski, CJ
通讯作者：
Bachurski, CJ
影响因子：
15.3
作者：
Graf, D;Nethisinghe, S;Merkenschlager, M
通讯作者：
Merkenschlager, M
影响因子：
4.4
作者：
Gutiérrez-Frías, C;Sacedon, R;Vicente, A
通讯作者：
Vicente, A