title: Gene expression profile of endotoxin-stimulated leukocytes of the term new born: control of cytokine gene expression by interleukin-10.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of Neonatal-Perinatal Medicine, Stony Brook Long Island Children's Hospital, Stony Brook, New York, United States of America. dennis.davidson@stonybrookmedicine.edu
authors: Dennis
authors: D
authors: Davidson
authors: Alla
authors: A
authors: Zaytseva
authors: Veronika
authors: V
authors: Miskolci
authors: Susana
authors: S
authors: Castro-Alcaraz
authors: Ivana
authors: I
authors: Vancurova
authors: Hardik
authors: H
authors: Patel
mesh_terms: D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D047929:Term Birth / Q000235:genetics*; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D004731:Endotoxins; C508609:IL10 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10