ST2 and IL-33 in pregnancy and pre-eclampsia.
ST2 and IL-33 in pregnancy and pre-eclampsia.
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妊娠和先兆子痫的ST2和IL-33。
DOI：
10.1371/journal.pone.0024463
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Sargent IL
中科院分区：
文献类型：
--
作者：
Granne I;Southcombe JH;Snider JV;Tannetta DS;Child T;Redman CW;Sargent IL
正常妊娠与轻微的全身炎症反应和对 2 型细胞因子产生的免疫偏向有关，而先兆子痫的特点是更强烈的炎症反应，与内皮功能障碍和 1 型细胞因子占主导地位有关。白细胞介素 (IL)-33 是 IL-1 家族的新成员，它与其受体 ST2L 结合以诱导 2 型细胞因子。 ST2 (sST2) 的可溶性变体充当诱饵受体来调节 IL-33 的活性。在这项研究中，测量了正常妊娠每个三个月和先兆子痫女性的循环 IL-33 和 sST2。虽然 IL-33 在正常妊娠期间或非妊娠、正常妊娠或先兆子痫妇女之间没有变化，但 sST2 发生了显着变化。 sST2 在正常妊娠晚期升高（p<0.001），在先兆子痫中进一步升高（p<0.001）。这种增加是在疾病发作之前出现的（p<0.01）。先兆子痫是一种由胎盘源性因素引起的疾病，我们发现在正常胎盘和先兆子痫胎盘的裂解物中都可以检测到 IL-33 和 ST2。在合体滋养层上鉴定出 ST2，但未鉴定出 IL-33，而 IL-33 在血管周围组织上表达。在体外胎盘灌注模型中，sST2由胎盘分泌到“母体”洗脱液中，并且用促炎细胞因子处理或受到缺氧/再灌注损伤的胎盘外植体释放更多的sST2，这表明先兆子痫女性中循环sST2量增加的至少一部分源自胎盘。这些结果表明，sST2 可能在妊娠并发先兆子痫中发挥重要作用，并且 sST2 增加可能导致该疾病出现 1 型偏倚。
Normal pregnancy is associated with a mild systemic inflammatory response and an immune bias towards type 2 cytokine production, whereas pre-eclampsia is characterized by a more intense inflammatory response, associated with endothelial dysfunction and a type 1 cytokine dominance. Interleukin (IL)-33 is a newly described member of the IL-1 family, which binds its receptor ST2L to induce type 2 cytokines. A soluble variant of ST2 (sST2) acts as a decoy receptor to regulate the activity of IL-33. In this study circulating IL-33 and sST2 were measured in each trimester of normal pregnancy and in women with pre-eclampsia. While IL-33 did not change throughout normal pregnancy, or between non-pregnant, normal pregnant or pre-eclamptic women, sST2 was significantly altered. sST2 was increased in the third trimester of normal pregnancy (p<0.001) and was further increased in pre-eclampsia (p<0.001). This increase was seen prior to the onset of disease (p<0.01). Pre-eclampsia is a disease caused by placental derived factors, and we show that IL-33 and ST2 can be detected in lysates from both normal and pre-eclampsia placentas. ST2, but not IL-33, was identified on the syncytiotrophoblast layer, whereas IL-33 was expressed on perivascular tissue. In an in vitro placental perfusion model, sST2 was secreted by the placenta into the ‘maternal’ eluate, and placental explants treated with pro-inflammatory cytokines or subjected to hypoxia/reperfusion injury release more sST2, suggesting the origin of at least some of the increased amounts of circulating sST2 in pre-eclamptic women is the placenta. These results suggest that sST2 may play a significant role in pregnancies complicated by pre-eclampsia and increased sST2 could contribute to the type 1 bias seen in this disorder.
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DOI：
10.1073/pnas.0812690106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Cayrol, Corinne;Girard, Jean-Philippe
通讯作者：
Girard, Jean-Philippe
影响因子：
3.4
作者：
Foidart, J. M.;Schaaps, J. P.;Lorquet, S.
通讯作者：
Lorquet, S.
DOI：
10.1006/bbrc.1997.6810
发表时间：
1997-06-27
影响因子：
3.1
作者：
Kumar, S;Tzimas, MN;Young, PR
通讯作者：
Young, PR
影响因子：
38.9
作者：
Brunner, M;Krenn, C;Ankersmit, HJ
通讯作者：
Ankersmit, HJ
DOI：
10.1164/ajrccm.164.2.2008120
发表时间：
2001-07-15
影响因子：
24.7
作者：
Oshikawa, K;Kuroiwa, K;Sugiyama, Y
通讯作者：
Sugiyama, Y