Differential Gene Expression Patterns by Oligonucleotide Microarray of Basal versus Lipopolysaccharide-Activated Monocytes from Cord Blood versus Adult Peripheral Blood

Abstract

Monocytes (Mo) are critically important in the generation of inflammatory mediators, cytokines/chemokines, and regulation of innate and adaptive immune responses. We and others have previously demonstrated significant dysregulated cytokine gene expression and protein production and in vitro functional activities of activated cord blood (CB) vs adult peripheral blood (APB) mononuclear cells (MNC). In this study, we compared, by oligonucleotide microarray, the differential gene expression profiles of basal and LPS-activated APB vs CB Mo. We demonstrated a significant increase in the gene expression of several important functional groups of CB genes compared with basal levels including cytokine (IL-12p40, 5-fold), immunoregulatory (signaling lymphocytic activation molecule, 4-fold), signal transduction (Pim-2, 3-fold), and cell structure (Rho7, 4-fold) among others. Furthermore, there was significantly differentially amplified gene expression in LPS-activated APB vs LPS-activated CB Mo, including cytokine (G-CSF, 14-fold), chemokine (macrophage-inflammatory protein 1alpha, 5-fold), immunoregulatory (MHC DRB1, 5-fold), transcription factor (JunB, 4-fold), signal transduction (STAT4, 5-fold), apoptotic regulation (BAX, 5-fold), and cell structure (ladinin 1, 6-fold) among others. These results provide insight into the molecular basis for normal genetic regulation of Mo development and cellular function and differential inflammatory and innate and adaptive immune responses between activated CB and APB Mo.

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.…”

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

“…Dembinski et al [30] observed a similar production of IL-8 in unstimulated whole blood of neonates and adults, but a significantly higher IL-8 expression in neonatal cells after stimulation with LPS. In contrast, Jiang et al [31] showed a higher IL-8 gene expression in LPS-activated monocytes in adult peripheral blood than in cord blood. IL-8 has been implicated in the development of persisting lung inflammation and chronic lung disease [32] .…”

Dysregulation of Expression of Immunoregulatory and Cytokine Genes and Its Association with the Immaturity in Neonatal Phagocytic and Cellular Immunity

“…This approach, however, of examining single gene differential regulation of activated CB versus APB MNC is time-consuming. To accelerate this analysis and to more comprehensively examine differential CB versus APB Mo gene expression patterns, we used oligonucleotide microarray technology to examine entire genome-wide gene expression profi les of Mo from CB and APB in the basal (constitutive state) and following LPS activation [97] . In this study, we demonstrated a signifi cant increase in the gene expression of several important functional groups of CB genes compared with basal levels including cytokine (IL-12 p40, 5-fold), immunoregulatory (signaling lymphocytic activation molecule, 4-fold), signal transduction (Pim-2, 3-fold), and cell structure (Rho7, 4-fold) among others.…”