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

• Published in: Bulletin of experimental biology and medicine Vol. 166; no. 4; pp. 473 - 476
• Main Authors: Gorskaya, Yu. F., Tukhvatulin, A. I., Dzharullaeva, A. Sh, Nesterenko, V. G.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2019; Springer; Springer Nature B.V
• Subjects: Acetylmuramyl-Alanyl-Isoglutamine - pharmacology; Animals; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cell Biology; Cloning; Drug Synergism; Immune response; Immunosuppression; Inflammation; Innate immunity; Interleukin 10; Internal Medicine; Laboratory Medicine; Ligands; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Male; Mesenchymal Stem Cells - drug effects; Mice; Muramyl dipeptide; NOD2 protein; Nod2 Signaling Adaptor Protein - agonists; Pathology; Peritoneum; Stromal cells; TLR4 protein; Toll-Like Receptor 4 - agonists; Toll-like receptors; Tumor necrosis factor-α; stromal cells; immune response; NLR and TLR ligands
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-019-04375-6

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.