Gene Expression Profiles of Adult Peripheral and Cord Blood Mononuclear Cells Altered by Lipopolysaccharide

Abstract

Background: Neonatal Gram-negative sepsis is often characterized by a fulminant clinical course, compared to adults, resulting in higher morbidity and mortality. Genome-wide gene expression analysis can provide insights into the molecular alterations in sepsis. Objectives: To evaluate in vitro activation of the neonatal and adult immune system, gene expression patterns were compared in mononuclear cells from cord (CBMNC) and adult peripheral blood (APBMNC). Methods: To better understand the influence of early molecular signals on the effects of sepsis, Affymetrix gene profiling (8,475 genes) was done on RNA isolated from CBMNC and APBMNC without and after incubation with 100 ng/ml lipopolysaccharide (LPS). Results: We demonstrated significant alterations in the expression of 108 CBMNC and APBMNC genes compared with basal levels, 188 significant changes in CBMNC and 97 in APBMNC, including cytokines, chemokines and immunoregulatory genes. Furthermore, we found 5 genes showing a significant interaction effect between cell type and LPS stimulation, including tumor necrosis factor receptor superfamily, member 6 (FAS), absent in melanoma 2, malic enzyme 1, hemoglobin Ε 1, and trans-prenyltransferase. Conclusions: These results provide further support for a marked difference in the pathogenesis of neonatal and adult sepsis and may stimulate additional studies to investigate some of the altered genes as potential new targets for diagnostic tools and therapeutic strategies.

Postnatal development of lipopolysaccharide-induced inflammatory response in the brain

“…These studies suggest that the neonatal immune cells are relatively immature compared to adult immune cells. Consistent with this, microarray studies comparing cord blood and adult PBMCs have shown significant differences in the expression of several signal transduction factors and transcription factors following LPS stimulation [34][35][36]. In addition, it has been shown that a higher serum level of adenosine, an endogenous purine metabolite with immunomodulatory properties, is associated with lower TNF-a production in response to Data were presented as mean ± SE; n = 4.…”

LPS- and LTA-Induced Expression of IL-6 and TNF-αin Neonatal and Adult Blood: Role of MAPKs and NF-κB

“…We have previously shown that stimulation of whole blood with LPS (100 ng/mL) induced a peak phosphorylation of p38 MAPK and NF- κ B within 15 min in both newborn and adult cells, with a significantly decreased activation of p38 MAPK in neonatal blood [16, 19]. The inhibition of LPS-induced p38 MAPK activation in neonatal and adult whole blood was associated with a strong reduction in the release of cytokines, whereas the pharmacological inhibition of NF- κ B showed no effect.…”

In vitro screening of LPS-induced miRNAs in leukocytes derived from cord blood and their possible roles in regulating TLR signals

“…Sepsis, which leads to severe adverse outcomes such as organ dysfunction and death, can develop when the host defensive response to an infection is magnified (3). In human cord blood (CB) mononuclear cells, this LPS-triggered activation of the proinflammatory response results in many dysregulated genes that have been previously characterized by genome-wide expression profiling methods (4).…”