Ligands of NOD2 (Muramyl Dipeptide) and TLR4 (LPS) in 24 h after Combined In Vivo Administration Produce a Synergistic Increase in the Content of Multipotent Stromal Cells in the Bone Marrow and Peritoneal Exudate of CBA Mice


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Abstract

In 24 h after combined administration of ligands of NOD2 (muramyl dipeptide) and TLR4 (LPS) receptors to CBA mice, a synergistic increase (by 10 times compared to the intact control) in cloning efficiency and content of multipotent stromal cells was observed in the bone marrow in comparison with the total effects of their individual administration (by 2.1 and 4.1 times, respectively). A similar effect was also observed in the peritoneal exudate. When ligands were administered simultaneously, the concentration of osteogenic multipotent stromal cells in the bone marrow decreased to a greater extent than in case of individual injections of the ligands, but did not drop below 7% of the control, which is apparently indicative of a decline threshold. In 3 h after simultaneous addition of the ligands in vitro to 12-day primary cultures of mouse bone marrow stromal cells, a synergistic increase in TNFα concentration was observed (32-fold increase from the level of intact control), while IL-10 concentration did not differ from the control, which is indicative of the proinflammatory nature of the process and the absence of immunosuppressive effect. These results suggest that activation of the stromal tissue depends on the intensity of innate immunity reactions.

About the authors

Yu. F. Gorskaya

Laboratory of Immunity Regulation and Immunological Tolerance

Author for correspondence.
Email: uliya.gorskaya@nearmedic.ru
Russian Federation, Moscow

A. I. Tukhvatulin

Laboratory of Cell Microbiology, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation

Email: uliya.gorskaya@nearmedic.ru
Russian Federation, Moscow

A. Sh. Dzharullaeva

Laboratory of Cell Microbiology, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation

Email: uliya.gorskaya@nearmedic.ru
Russian Federation, Moscow

V. G. Nesterenko

Laboratory of Immunity Regulation and Immunological Tolerance

Email: uliya.gorskaya@nearmedic.ru
Russian Federation, Moscow

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