Progesterone treatment enhances the expansion of placental immature myeloid cells in a mouse model of premature labor
Progesterone treatment enhances the expansion of placental immature myeloid cells in a mouse model of premature labor
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DOI：
10.1016/j.jri.2018.10.003
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发表时间：
2019-02-01
影响因子：
3.4
通讯作者：
Fainaru, Ofer
中科院分区：
文献类型：
--
作者：
Gutzeit, Ola;Segal, Linoy;Fainaru, Ofer
简介：未成熟髓样细胞（IMC）是促血管生成骨髓（BM）衍生的细胞，其通常分化成炎性细胞，例如嗜中性粒细胞、单核细胞和树突细胞（DC）。我们的特点是胎盘IMCs比较他们的基因表达和亚群的肿瘤IMCs，并测试我们的假设，孕激素抑制早产，可能会影响他们的丰度和differentiation.Methods：之间的差异IMC亚群在皮下肿瘤与胎盘C57 BL/6或ICR（CD-1）小鼠进行了分析，流式细胞术和基因表达的微阵列检测。BM和胎盘细胞与或不与孕酮一起孵育，并分析IMC亚群。对于早产诱导孕鼠预处理或不与孕激素处理或不与脂多糖（LPS）。结果：我们检测到富集的粒细胞-IMCs在胎盘相比，肿瘤，减少单核细胞-IMCs。胎盘与肿瘤IMCs的mRNA表达揭示了深刻的转录改变。孕激素处理的BM-CD 11b（+）细胞离体诱导粒细胞-IMC的富集和单核细胞-IMC和DC的减少。LPS治疗在体内导致增加BM-IMC在孕酮预处理或未预处理的小鼠。在胎盘LPS减少IMC人口，而孕激素导致完全废除这种effect.Discussion：胎盘IMCs不同的肿瘤IMCs在两个亚群和基因表达。孕酮增强离体胎盘特异性粒细胞IMCs的增殖，LPS诱导的分娩仅在孕酮未预处理的小鼠中伴随胎盘IMCs的减少。因此，我们推测孕酮在预防早产中的保护作用可能至少部分地由这种特异性抗炎作用来解释。
Introduction: immature-myeloid cells (IMCs) are proangiogenic bone marrow (BM)-derived cells that normally differentiate into inflammatory cells such as neutrophils, monocytes and dendritic cells (DCs). We characterized placental IMCs comparing their gene expression and subpopulations to tumor IMCs, and tested our hypothesis that progesterone that inhibits preterm labor, may affect their abundance and differentiation.Methods: differences between IMC-subpopulations in subcutaneous tumors versus placentas in C57BL/6 or ICR (CD-1) mice were analyzed by flow cytometry and gene expression was detected by microarrays. BM- and placental cells were incubated with or without progesterone and IMC subpopulations were analyzed. For preterm labor induction pregnant mice pretreated or not with progesterone were or were not treated with Lipopolysaccharide (LPS).Results: we detected enrichment of granulocytic-IMCs in placentas compared to tumors, paralleled by a decrease in monocytic-IMCs. mRNA expression of placenta- versus tumor IMCs revealed profound transcriptional alterations. Progesterone treated BM-CD11b(+) cells ex-vivo induced enrichment of granulocytic-IMCs and a decrease in monocytic-IMCs and DCs. LPS treatment in-vivo led to an increase in BM-IMCs in both progesterone pretreated or non-pretreated mice. In the placenta LPS decreased the IMC population while progesterone led to complete abrogation of this effect.Discussion: placental IMCs differ from tumor-IMCs in both subpopulations and gene expression. Progesterone enhances the proliferation of placenta-specific granulocytic IMCs ex-vivo and LPS induced labor is accompanied by a decrease in placental IMCs only in progesterone non-pretreated mice. We thus speculate that the protective effect of progesterone in preventing preterm labor may be explained at least in part by this specific anti-inflammatory effect.