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.