Division of Neonatal-Perinatal Medicine, Stony Brook Long Island Children's Hospital, Stony Brook, New York, United States of America.
PLoS One. 2013;8(1):e53641. doi: 10.1371/journal.pone.0053641. Epub 2013 Jan 11.
Increasing evidence now supports the association between the fetal inflammatory response syndrome (FIRS) with the pathogenesis of preterm labor, intraventricular hemorrhage and bronchopulmonary dysplasia. Polymorphonuclear leukocyte (PMNs) and mononuclear cell (MONOs) infiltration of the placenta is associated with these disorders. The aim of this study was to reveal cell-specific differences in gene expression and cytokine release in response to endotoxin that would elucidate inflammatory control mechanisms in the newly born.
PMNs and MONOs were separately isolated from the same cord blood sample. A genome-wide microarray screened for gene expression and related pathways at 4 h of LPS stimulation (n = 5). RT-qPCR and ELISA were performed for selected cytokines at 4 h and 18 h of LPS stimulation.
Compared to PMNs, MONOs had a greater diversity and more robust gene expression that included pro-inflammatory (PI) cytokines, chemokines and growth factors at 4 h. Only MONOs had genes changing expression (all up regulated including interleukin-10) that were clustered in the JAK/STAT pathway. Pre-incubation with IL-10 antibody, for LPS-stimulated MONOs, led to up regulated PI and IL-10 gene expression and release of PI cytokines after 4 h.
The present study suggests a dominant role of MONO gene expression in control of the fetal inflammatory response syndrome at 4 hrs of LPS stimulation. LPS-stimulated MONOs but not PMNs of the newborn have the ability to inhibit PI cytokine gene expression by latent IL-10 release.
越来越多的证据支持胎儿炎症反应综合征（FIRS）与早产、脑室内出血和支气管肺发育不良的发病机制有关。多形核白细胞（PMN）和单核细胞（MONO）浸润胎盘与这些疾病有关。本研究旨在揭示内毒素刺激后基因表达和细胞因子释放的细胞特异性差异，阐明新生儿炎症控制机制。
从同一脐血样本中分别分离 PMN 和 MONO。在 LPS 刺激 4 小时（n=5）进行全基因组微阵列筛选基因表达和相关途径。在 LPS 刺激 4 小时和 18 小时进行 RT-qPCR 和 ELISA 以检测选定细胞因子。
与 PMN 相比，MONO 在 4 小时时具有更大的多样性和更强烈的基因表达，包括促炎（PI）细胞因子、趋化因子和生长因子。只有 MONO 具有改变表达的基因（所有上调，包括白细胞介素-10），这些基因聚类在 JAK/STAT 途径中。用 IL-10 抗体预处理 LPS 刺激的 MONO 后，在 4 小时后导致 PI 和 IL-10 基因表达上调和 PI 细胞因子释放。
本研究表明，在 LPS 刺激 4 小时时，MONO 的基因表达在控制胎儿炎症反应综合征中起主导作用。LPS 刺激的 MONO 而不是新生儿的 PMN 具有通过潜在的 IL-10 释放抑制 PI 细胞因子基因表达的能力。
