Placental CX3CL1 is Deregulated by Angiotensin II and Contributes to a Pro-Inflammatory Trophoblast-Monocyte Interaction
Placental CX3CL1 is Deregulated by Angiotensin II and Contributes to a Pro-Inflammatory Trophoblast-Monocyte Interaction
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DOI：
10.3390/ijms20030641
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发表时间：
2019-02-01
影响因子：
5.6
通讯作者：
Gauster, Martin
中科院分区：
文献类型：
--
作者：
Nonn, Olivia;Guettler, Jacqueline;Gauster, Martin
CX3CL1 是一种参与人类妊娠许多方面的趋化因子，是一种膜结合趋化因子，以可溶性亚型形式进入循环系统。胎盘 CX3CL1 由炎症细胞因子诱导，在严重的早发性先兆子痫中表达上调。在本研究中，探讨了血管紧张素 II 是否可以解除胎盘 CX3CL1 表达的调节，以及 CX3CL1 是否可以促进单核细胞的促炎症状态的假设。对人胎盘样本 (n = 45) 的 qPCR 分析显示，CX3CL1 和血管紧张素 II 受体 AGTR1 在整个妊娠早期稳定表达，但未显示母亲年龄、BMI 和胎龄两者或任何影响之间的相关性。胎盘外植体的血管紧张素 II 孵育暂时解除了 CX3CL1 表达的调节，而血管紧张素 II 受体拮抗剂坎地沙坦则逆转了这种效应。在 SGHPL-4 滋养层中重组人 CX3CL1 的过表达增加了 THP-1 单核细胞的粘附，并在与人原代单核细胞共培养时显着增加了 IL8、CCL19 和 CCL13。原代单核细胞与 CX3CL1 的孵育以及随后的 CD16(+) 亚群的全局转录组分析揭示了 81 个上调的基因，包括 clusterin、lipocalin-2 和瘦素受体。醛固酮合酶、骨桥蛋白和可的松还原酶是存在的 66 个下调基因中的一些。这些数据表明母体血管紧张素 II 水平影响胎盘 CX3CL1 表达，进而影响单核细胞与滋养层的粘附。胎盘CX3CL1的释放可以促进母体单核细胞CD16(+)亚群的促炎状态。
CX3CL1, which is a chemokine involved in many aspects of human pregnancy, is a membrane-bound chemokine shed into circulation as a soluble isoform. Placental CX3CL1 is induced by inflammatory cytokines and is upregulated in severe early-onset preeclampsia. In this study, the hypothesis was addressed whether angiotensin II can deregulate placental CX3CL1 expression, and whether CX3CL1 can promote a pro-inflammatory status of monocytes. qPCR analysis of human placenta samples (n = 45) showed stable expression of CX3CL1 and the angiotensin II receptor AGTR1 throughout the first trimester, but did not show a correlation between both or any influence of maternal age, BMI, and gestational age. Angiotensin II incubation of placental explants transiently deregulated CX3CL1 expression, while the angiotensin II receptor antagonist candesartan reversed this effect. Overexpression of recombinant human CX3CL1 in SGHPL-4 trophoblasts increased adhesion of THP-1 monocytes and significantly increased IL8, CCL19, and CCL13 in co-cultures with human primary monocytes. Incubation of primary monocytes with CX3CL1 and subsequent global transcriptome analysis of CD16(+) subsets revealed 81 upregulated genes, including clusterin, lipocalin-2, and the leptin receptor. Aldosterone synthase, osteopontin, and cortisone reductase were some of the 66 downregulated genes present. These data suggest that maternal angiotensin II levels influence placental CX3CL1 expression, which, in turn, can affect monocyte to trophoblast adhesion. Release of placental CX3CL1 could promote the pro-inflammatory status of the CD16(+) subset of maternal monocytes.