Abstract
IntroductionIncreasing 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.MethodsPMNs 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.ResultsCompared 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.DiscussionThe 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.
Highlights
Increasing evidence supports the association between the fetal inflammatory response syndrome (FIRS) with the pathogenesis of preterm labor, intraventricular hemorrhage and bronchopulmonary dysplasia (BPD) [1,2,3]
Gene expression changes in polymorphonuclear leukocytes (PMNs) and MONOs from 5 newborns were detected by the genome-wide microarray after 4 h of LPS stimulation
PMNs and MONOs play a pivotal role in development of FIRS and BPD as well as preterm delivery and intraventricular hemorrhage [5,20]
Summary
Increasing evidence 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. Increasing evidence supports the association between the fetal inflammatory response syndrome (FIRS) with the pathogenesis of preterm labor, intraventricular hemorrhage and bronchopulmonary dysplasia (BPD) [1,2,3]. The pathogenesis of FIRS involves inflammation by innate immune cells, principally polymorphonuclear leukocytes (PMNs) and monocytes (MONOs) [1,5]. In experimental models of premature lung disease, intra-amniotic administration of LPS accelerates lung surfactant but causes a persistent lung inflammation as seen in BPD [9]. Bronchopulmonary dysplasia is one of the major causes of mortality and morbidity in neonatal period
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