Yan Huan, Li Hong, Zhu Linlin, Gao Junjun, Li Pengyun, Zhang Zhan
a Department of Obstetrics and Gynecology , the Third Affiliated Hospital of Zhengzhou University , Zhengzhou , China.
b Department of Pathology and Laboratory Medicine , University of Tennessee Health Science Center , Memphis , TN , USA.
J Matern Fetal Neonatal Med. 2019 Sep;32(18):2961-2969. doi: 10.1080/14767058.2018.1452903. Epub 2018 Mar 25.
Increased inflammation is considered as a risk factor and a promoter of preterm birth (PTB). Monocytes and neutrophils are the main sources of cytokines in the early inflammatory phase. So far, very few studies have indicated CD14/TLR4 and TREM-1 on the monocytes and neutrophils as important targets in PTB. TLR4 and TREM-1 on CD14 maternal and cord blood monocytes and neutrophils were detected using flow cytometry in 48 normal term women, 48 PTB with chorioamnionitis (CCA) women, and 40 PTB without CCA women. In the fetal membranes, mRNA and protein levels of the CD14/TLR4-TREM-1 signaling pathway, CD14, TLR4, NF-κBp65, and TREM-1 were analyzed by qRT-PCR and western blot. ELISA was further used to detect TLR4 and TREM-1 levels in maternal and cord serums. Compared with the normal term and PTB without CCA women, we found that (1) TLR4 and TREM-1 levels on CD14 maternal and cord blood monocytes and neutrophils in the PTB with CCA group were elevated ( < .001); (2) the protein and mRNA expressions of CA14, TLR4, NF-κBp65, and TREM-1 of the PTB with CCA group were upregulated ( < .001); (3) Maternal and cord serum concentrations of TLR4 and TREM-1 in the PTB with CCA group were greater ( < .001). The high levels of TLR4 and TREM-1 surface expression were observed on CD14 maternal and cord blood monocyte and neutrophils, confirming their proinflammatory profiles in PTB with CCA. TLR4 and TREM-1 on monocyte and neutrophils might have a role in infection-related PTB.
炎症增加被认为是早产（PTB）的一个危险因素和促进因素。单核细胞和中性粒细胞是早期炎症阶段细胞因子的主要来源。到目前为止，很少有研究表明单核细胞和中性粒细胞上的CD14/TLR4和TREM-1是早产中的重要靶点。使用流式细胞术检测了48名足月正常孕妇、48名患有绒毛膜羊膜炎（CCA）的早产孕妇和40名无CCA的早产孕妇母血和脐血单核细胞及中性粒细胞上的TLR4和TREM-1。在胎膜中，通过qRT-PCR和蛋白质印迹分析了CD14/TLR4-TREM-1信号通路、CD14、TLR4、NF-κBp65和TREM-1的mRNA和蛋白质水平。进一步采用ELISA检测母血和脐血血清中的TLR4和TREM-1水平。与足月正常孕妇和无CCA的早产孕妇相比，我们发现：（1）患有CCA的早产组母血和脐血单核细胞及中性粒细胞上的TLR4和TREM-1水平升高（<0.001）；（2）患有CCA的早产组CA14、TLR4、NF-κBp65和TREM-1的蛋白质和mRNA表达上调（<0.001）；（3）患有CCA的早产组母血和脐血血清中TLR4和TREM-1的浓度更高（<0.001）。在母血和脐血单核细胞及中性粒细胞上观察到TLR4和TREM-1的高水平表面表达，证实了它们在患有CCA的早产中的促炎特征。单核细胞和中性粒细胞上的TLR4和TREM-1可能在感染相关的早产中起作用。
