Uric acid induces trophoblast IL-1β production via the inflammasome: implications for the pathogenesis of preeclampsia.
Uric acid induces trophoblast IL-1β production via the inflammasome: implications for the pathogenesis of preeclampsia.
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DOI：
10.1111/j.1600-0897.2010.00960.x
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Abrahams VM
中科院分区：
文献类型：
--
作者：
Mulla MJ;Myrtolli K;Potter J;Boeras C;Kavathas PB;Sfakianaki AK;Tadesse S;Norwitz ER;Guller S;Abrahams VM
先兆子痫与高尿酸血症有关，高尿酸血症与疾病的严重程度相关。循环尿酸水平在临床表现前升高，提示它们可能有因果关系。尿酸或尿酸钠激活结节样受体NALP3，导致炎症小体激活和IL-1β的处理。由于子痫前期与胎盘免疫/炎症调节失调有关，我们试图确定滋养细胞中NALP3炎症体的存在，以及MSU对其激活的影响。分离的妊娠早期和晚期滋养层细胞检测炎性小体成分NALP1、NALP3和ASC的表达。将早孕滋养层细胞与MSU或不加MSU孵育后，测定IL-1β的分泌、加工及半胱氨酸天冬氨酸氨基转移酶-1活性。滋养层细胞在基础条件下表达Nalp1、NALP3和ASC。经MSU孵育后，早孕滋养层细胞IL-1β分泌上调。这与活化的IL-1β和活化的caspase-1的表达水平升高有关。Asc基因敲除可减少MSU诱导的IL-1β的分泌。这些发现表明，尿酸激活滋养层细胞中的炎性小体，导致IL-1β的产生。这可能为在母胎界面诱导炎症导致胎盘功能障碍和包括先兆子痫在内的不良妊娠结局提供一种新的机制。
Preeclampsia is associated with hyperuricemia, which correlates with the disease severity. Levels of circulating uric acid increase before the clinical manifestations, suggesting they may be causally related. Uric acid, or monosodium urate (MSU), activates the Nod-like receptor, Nalp3, leading to inflammasome activation and IL-1β processing. Since preeclampsia is associated with placental immune/inflammatory dysregulation, we sought to determine in the trophoblast, the presence of the Nalp3 inflammasome, and the effect of MSU on its activation. Isolated first and third trimester trophoblast were assessed for expression of the inflammasome components, Nalp1, Nalp3 and ASC. First trimester trophoblast cells were incubated with or without MSU, after which, IL-1β secretion and processing and caspase-1 activation was determined. Trophoblast cells expressed Nalp1, Nalp3 and ASC under basal conditions. Following incubation with MSU, first trimester trophoblast IL-1β secretion was upregulated. This correlated with increased expression levels of active IL-1β and active caspase-1. ASC knockdown reduced MSU-induced IL-1β secretion. These findings demonstrate that uric acid activates the inflammasome in the trophoblast, leading to IL-1β production. This may provide a novel mechanism for the induction of inflammation at the maternal-fetal interface leading to placental dysfunction and adverse pregnancy outcome, including preeclampsia.
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影响因子：
8.7
作者：
Franchi L;Warner N;Viani K;Nuñez G
通讯作者：
Nuñez G
DOI：
10.1016/0960-0760(93)90202-8
发表时间：
1993-07-01
影响因子：
4.1
作者：
GULLER, S;LACROIX, NC;LOCKWOOD, CJ
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LOCKWOOD, CJ
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32.4
作者：
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Tschopp, J
影响因子：
9.1
作者：
Jin, Chengcheng;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
5.4
作者：
Funai, EF;Friedlander, Y;Harlap, S
通讯作者：
Harlap, S