人胎盘中的白细胞介素-33
Interleukin-33 in the human placenta.
作者信息
Topping Vanessa, Romero Roberto, Than Nandor Gabor, Tarca Adi L, Xu Zhonghui, Kim Sun Young, Wang Bing, Yeo Lami, Kim Chong Jai, Hassan Sonia S, Kim Jung-Sun
机构信息
Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD 20892, USA.
出版信息
J Matern Fetal Neonatal Med. 2013 Mar;26(4):327-38. doi: 10.3109/14767058.2012.735724. Epub 2012 Nov 23.
OBJECTIVE
Interleukin-33 (IL-33) is the newest member of the IL-1 cytokine family, a group of key regulators of inflammation. The purpose of this study was to determine whether IL-33 is expressed in the human placenta and to investigate its expression in the context of acute and chronic chorioamnionitis.
METHODS
Placental tissues were obtained from five groups of patients: 1) normal pregnancy at term without labor (n = 10); 2) normal pregnancy at term in labor (n = 10); 3) preterm labor without inflammation (n = 10); 4) preterm labor with acute chorioamnionitis and funisitis (n = 10); and 5) preterm labor with chronic chorioamnionitis (n = 10). Immunostaining was performed to determine IL-33 protein expression patterns in the placental disk, chorioamniotic membranes, and umbilical cord. mRNA expression of IL-33 and its receptor IL1RL1 (ST2) was measured in primary amnion epithelial and mesenchymal cells (AECs and AMCs, n = 4) and human umbilical vein endothelial cells (HUVECs, n = 4) treated with IL-1β (1 and 10 ng/ml) and CXCL10 (0.5 and 1 or 5 ng/ml).
RESULTS
- Nuclear IL-33 expression was found in endothelial and smooth muscle cells in the placenta, chorioamniotic membranes, and umbilical cord; 2) IL-33 was detected in the nucleus of CD14+ macrophages in the chorioamniotic membranes, chorionic plate, and umbilical cord, and in the cytoplasm of myofibroblasts in the Wharton's jelly; 3) acute (but not chronic) chorioamnionitis was associated with the presence of IL-33+ macrophages in the chorioamniotic membranes and umbilical cord; 4) expression of IL-33 or IL1RL1 (ST2) mRNA in AECs was undetectable; 5) IL-33 mRNA expression increased in AMCs and HUVECs after IL-1β treatment but did not change with CXCL10 treatment; and 6) IL1RL1 (ST2) expression decreased in AMCs and increased in HUVECs after IL-1β but not CXCL10 treatment.
CONCLUSIONS
IL-33 is expressed in the nucleus of placental endothelial cells, CD14+ macrophages, and myofibroblasts in the Wharton's jelly. IL-1β can induce the expression of IL-33 and its receptor. Protein expression of IL-33 is detectable in macrophages of the chorioamniotic membranes in acute (but not chronic) chorioamnionitis.
目的
白细胞介素-33（IL-33）是白细胞介素-1细胞因子家族的最新成员，该家族是炎症的一组关键调节因子。本研究的目的是确定IL-33是否在人胎盘中表达，并研究其在急性和慢性绒毛膜羊膜炎中的表达情况。
方法
从五组患者中获取胎盘组织：1）足月未临产的正常妊娠（n = 10）；2）足月临产的正常妊娠（n = 10）；3）无炎症的早产（n = 10）；4）伴有急性绒毛膜羊膜炎和脐带炎的早产（n = 10）；5）伴有慢性绒毛膜羊膜炎的早产（n = 10）。进行免疫染色以确定胎盘盘、绒毛膜羊膜和脐带中IL-33蛋白的表达模式。在经白细胞介素-1β（1和10 ng/ml）和CXC趋化因子配体10（0.5、1或5 ng/ml）处理的原代羊膜上皮和间充质细胞（AEC和AMC，n = 4）以及人脐静脉内皮细胞（HUVEC，n = 4）中测量IL-33及其受体IL1RL1（ST2）的mRNA表达。
结果
1）在胎盘、绒毛膜羊膜和脐带的内皮细胞和平滑肌细胞中发现了核IL-33表达；2）在绒毛膜羊膜、绒毛板和脐带的CD14+巨噬细胞核中以及华通胶中成肌纤维细胞的细胞质中检测到IL-33；3）急性（而非慢性）绒毛膜羊膜炎与绒毛膜羊膜和脐带中IL-33+巨噬细胞的存在有关；4）在AEC中未检测到IL-33或IL1RL1（ST2）mRNA的表达；5）白细胞介素-1β处理后，AMC和HUVEC中IL-33 mRNA表达增加，但CXC趋化因子配体10处理后未改变；6）白细胞介素-1β处理后，AMC中IL1RL1（ST2）表达降低，HUVEC中增加，但CXC趋化因子配体10处理后未改变。
结论
IL-33在胎盘内皮细胞、CD14+巨噬细胞和华通胶中成肌纤维细胞的细胞核中表达。白细胞介素-1β可诱导IL-33及其受体的表达。在急性（而非慢性）绒毛膜羊膜炎的绒毛膜羊膜巨噬细胞中可检测到IL-33的蛋白表达。
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