Erichment of Extracellular DNA from the Cultivation Medium of Human Peripheral Blood Mononuclears with Genomic CpG Rich Fragments Results in Increased Cell Production of IL-6 and TNFα via Activation of the NF-κB Signaling Pathway

摘要

Previously, it was found that blood plasma extracellular DNA (ecDNA) of patients with rheumatoid arthritis (RA) is enriched with CpG-rich genomic DNA fragments, which contain TLR9 ligands (Veiko et al., 2006). In this study we have demonstrated that ecDNA of a RA patient and model fragments added to a cultivation medium of peripheral blood mononuclear cells (PBMC) of healthy donors stimulate expression of genes for the TLR9-MyD88-NFkB-signaling pathway; this leads to a significant increase in concentrations of the proinflammatory cytokines IL-6 and TNFα in the cultivation medium. Human genomic DNA non-enriched with the CpG sequences did not stimulate IL-6 and TNFα synthesis in PBMC. A scheme explaining the potential role ecDNA in the induction and maintenance of increased levels of the proinflammatory cytokines under conditions damaging the human cells has been proposed.