The National Institutes of Health, Bethesda, Maryland, USA.
BMC Pregnancy Childbirth. 2010 Oct 21;10:66. doi: 10.1186/1471-2393-10-66.
Localized inflammation and increased expression of TLR4 receptors within the uterus has been implicated in the pathogenesis of preterm labor. It remains unclear whether intrauterine inflammatory responses activate the maternal peripheral circulatory system. Therefore we determined whether increased TLR4 expression is present in the peripheral maternal white blood cells of women with spontaneous preterm labor.
This is a cross-sectional study of 41 preterm labor cases and 41 non-preterm controls. For each case and control sample, RNA was purified from white blood cells and TLR4 mRNA pool size was evaluated by quantitative PCR. Protein expression levels were determined by flow cytometry. Statistical evaluation using multiple linear regressions was used to determine any significant differences between the cases and controls. The purpose was to determine association prevalence of TLR4 levels and preterm labor.
Adjusted mean TLR4 mRNA levels of 0.788 ± 0.037 (standard error) for preterm labor and 0.348 ± 0.038 for the corresponding pregnant control women were statistically significantly different (P = 0.002). Using the lower 95% confidence interval of the mean expression level in PTL subjects (0.7) as a cutoff value for elevated TLR4 mRNA levels, 25/41 (60.9%) of PTL patients expressed elevated TLR4 mRNA as compared to 0/41 (0%) in control subjects. The TLR4 receptor levels in the granulocyte fraction of white blood cells from preterm labor and pregnant controls were similar. However, TLR4+/CD14+monocytes were 2.3 times more frequent (70% vs. 30%) and TLR4 also had a 2.6-fold higher density (750 vs. 280 molecules per cell) in preterm labor women compared with pregnant controls. There was no difference in the levels of TLR4 in patients at term.
Patients with preterm labor exhibited elevated levels of CD14+ maternal blood monocytes each bearing enhanced expression of TLR4, indicating that the peripheral circulatory system is activated in patients with preterm labor. Elevated leukocyte TLR4 levels may be a useful biomarker associated with preterm labor.
局部炎症和 TLR4 受体在子宫内的表达增加，与早产的发病机制有关。目前尚不清楚宫内炎症反应是否会激活母体外周循环系统。因此，我们确定了自发性早产妇女外周血白细胞中 TLR4 表达是否增加。
这是一项前瞻性研究，纳入 41 例早产病例和 41 例非早产对照组。对于每个病例和对照样本，从白细胞中提取 RNA，通过定量 PCR 评估 TLR4 mRNA 池大小。通过流式细胞术测定蛋白表达水平。采用多元线性回归进行统计评估，以确定病例组和对照组之间是否存在显著差异。目的是确定 TLR4 水平与早产的关联患病率。
调整后的早产组 TLR4 mRNA 平均水平为 0.788 ± 0.037（标准误差），相应的妊娠对照组为 0.348 ± 0.038，两组间差异有统计学意义（P = 0.002）。以早产组中 TLR4 mRNA 表达水平的下 95%置信区间（0.7）作为 TLR4 mRNA 水平升高的截断值，41 例早产患者中有 25 例（60.9%）表达升高的 TLR4 mRNA，而对照组中无一例（0%）表达升高。早产组和对照组白细胞粒细胞部分的 TLR4 受体水平相似。然而，与妊娠对照组相比，TLR4+/CD14+单核细胞的频率高 2.3 倍（70%比 30%），TLR4 的密度高 2.6 倍（每个细胞 750 个比 280 个分子）。足月患者的 TLR4 水平无差异。
早产患者表现出 CD14+母血单核细胞水平升高，每个细胞均增强表达 TLR4，提示早产患者外周循环系统被激活。白细胞 TLR4 水平升高可能是与早产相关的有用生物标志物。
