Uric Acid Crystals Induce Placental Inflammation and Alter Trophoblast Function via an IL-1-Dependent Pathway: Implications for Fetal Growth Restriction.
Uric Acid Crystals Induce Placental Inflammation and Alter Trophoblast Function via an IL-1-Dependent Pathway: Implications for Fetal Growth Restriction.
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DOI：
10.4049/jimmunol.1601179
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发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Girard S
中科院分区：
文献类型：
--
作者：
Brien ME;Duval C;Palacios J;Boufaied I;Hudon-Thibeault AA;Nadeau-Vallée M;Vaillancourt C;Sibley CP;Abrahams VM;Jones RL;Girard S
胎盘过度炎症与几种病理情况有关，包括死产和胎儿生长受限(FGR)。虽然感染是炎症的已知原因，但相当大比例的怀孕有炎症的证据，而没有任何可检测到的感染。炎症也可以由内源性介质触发，称为损伤相关分子模式(DAMPS)或警报。尿酸是其中的一种，在病理性怀孕时，母体循环中的尿酸会增加，是已知的Nlrp3炎症体的激动剂和炎症的诱导者。然而，它在胎盘内和对妊娠结局的影响在很大程度上仍不清楚。我们发现尿酸晶体(尿酸单钠，MSU，晶体)诱导分离的人足月细胞滋养层细胞的促炎作用，主要分泌IL-1β和IL-6，这一结果在人足月胎盘外植体中得到证实。使用caspase-1抑制剂(抑制IL-1成熟)和IL-1ra(抑制IL-1信号)，MSU晶体的促炎作用被证明是IL-1依赖的。MSU晶体的抗炎作用伴随着滋养层细胞的凋亡和合体细胞的减少。相应地，在妊娠晚期给大鼠服用MSU晶体会引起胎盘炎症，并与胎儿生长受限有关。这些结果有力地证明了MSU晶体在病理性妊娠的母胎界面上具有积极的促炎作用，并强调了IL-1的关键调节作用。此外，我们的研究描述了一种新的妊娠期非感染性炎症的体内动物模型，该模型由MSU晶体触发，并导致胎儿生长减慢。
Excessive placental inflammation is associated with several pathological conditions, including stillbirth and fetal growth restriction (FGR). While infection is a known cause of inflammation, a significant proportion of pregnancies have evidence of inflammation without any detectable infection. Inflammation can also be triggered by endogenous mediators, called damage associated molecular pattern (DAMPs) or alarmins. One of these DAMPs, uric acid is increased in the maternal circulation in pathological pregnancies and is a known agonist of the Nlrp3 inflammasome and inducer of inflammation. However its effects within the placenta and on pregnancy outcome remain largely unknown. We found that uric acid crystals (monosodium urate, MSU, crystals) induces a pro-inflammatory profile in isolated human term cytotrophoblast cells, with a predominant secretion of IL-1β and IL-6, a result confirmed in human term placental explants. Pro-inflammatory effects of MSU crystals were shown to be IL-1-dependent using a caspase-1 inhibitor (inhibits IL-1 maturation) and IL-1Ra (inhibits IL-1 signaling). The pro-inflammatory effect of MSU crystals was accompanied by trophoblast apoptosis and decreased syncytialisation. Correspondingly, administration of MSU crystals to rats during late gestation induced placental inflammation and was associated with fetal growth restriction. These results make a strong case for an active pro-inflammatory role of MSU crystals at the maternal-fetal interface in pathological pregnancies, and highlight a key mediating role of IL-1. Furthermore, our study describes a novel in vivo animal model of non-infectious inflammation during pregnancy, which is triggered by MSU crystals and leads to reduced fetal growth.
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影响因子：
3.2
作者：
Laughon, S. Katherine;Catov, Janet;Powers, Robert W.;Roberts, James M.;Gandley, Robin E.
通讯作者：
Gandley, Robin E.
DOI：
10.1111/j.1600-0897.2010.00960.x
发表时间：
2011-06
期刊：
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子：
--
作者：
Mulla MJ;Myrtolli K;Potter J;Boeras C;Kavathas PB;Sfakianaki AK;Tadesse S;Norwitz ER;Guller S;Abrahams VM
通讯作者：
Abrahams VM
DOI：
10.1111/aji.12274
发表时间：
2014-10
期刊：
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子：
--
作者：
Girard S;Heazell AE;Derricott H;Allan SM;Sibley CP;Abrahams VM;Jones RL
通讯作者：
Jones RL
影响因子：
4.4
作者：
Liu, Hongqi;Redline, Raymond W.;Han, Yiping W.
通讯作者：
Han, Yiping W.
影响因子：
9.8
作者：
Girard, Sylvie;Tremblay, Luc;Sebire, Guillaume
通讯作者：
Sebire, Guillaume