Enrichment 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 TNF-a via activation of the NF-kB signaling pathway

   
Speranskii A.I.1, Kostyuk S.V.2, Kalashnikova E.A.3, Veiko N.N.2

1. Nasonova Research Institute of Rheumatology, Moscow, Russia
2. Research Centre of Medical Genetics (RCMG), Moscow, Russia
3. Moscow Regional Research Institute of Obstetrics and Gynecology, Moscow, Russia
Section: Clinical and Diagnostic Research
DOI: 10.18097/PBMC20166203331      PubMed Id: 27420628
Year: 2016  Volume: 62  Issue: 3  Pages: 331-340
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–NF-kB signaling pathway; this leads to a significant increase in concentrations of the proinflammatory cytokines IL-6 and TNF-a in the cultivation medium. Human genomic DNA non-enriched with the CpG sequences did not stimulate IL-6 and TNF-a 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.
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Keywords: rheumatoid arthritis (RA), extracellular DNA (ecDNA), TLR9, NF-kB
Citation:

Speranskii, A. I., Kostyuk, S. V., Kalashnikova, E. A., Veiko, N. N. (2016). Enrichment 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 TNF-a via activation of the NF-kB signaling pathway. Biomeditsinskaya khimiya, 62(3), 331-340.
This paper is also available as the English translation: 10.1134/S1990750815020122
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