Skip to main content
Log in

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:
Bulletin of Experimental Biology and Medicine Aims and scope

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Gorskaya YF, Danilova TA, Grabko VI, Nesterenko VG. Successive Administration of Streptococcus Type 5 Group A Antigens and S. typhimurium Antigenic Complex Corrects Elevation of Serum Cytokine Concentration and Number of Bone Marrow Stromal Pluripotent Cells in CBA Mice Induced by Each Antigen Separately. Bull. Exp. Biol. Med. 2015;160(2):256-259.

    Article  CAS  PubMed  Google Scholar 

  2. Gorskaya YF, Danilova TA, Karyagina AS, Lunin VG, Grabko VI, Bartov MS, Gromov AV, Grunina TM, Soboleva LA, Shapoval IM, Nesterenko VG. Effects of combined treatment with complex S. typhimurium antigens and factors stimulating osteogenesis (curettage, BMP-2) on multipotent bone marrow stromal cells and serum concentration of cytokines in CBA mice. Bull. Exp. Biol. Med. 2015;158(4):465-470.

    Article  CAS  PubMed  Google Scholar 

  3. Gorskaya UF, Danilova TA, Mezentzeva MV, Shapoval MM, Nesterenko VG. Effect of immunization with polyvinylpyrrolidone on the counts of stromal precursor cells in bone marrow and spleen of CBA and CBA/N mice and cytokine gene expression in primary cultures of these cells. Bull. Exp. Biol. Med. 2012;153(1):64-67.

    Article  CAS  PubMed  Google Scholar 

  4. Gorskaya YF, Tukhvatulin AI, Nesterenko VG. NLR2 and TLR3, TLR4, TLR5 Ligands, Injected In Vivo, Improve after 1 h the Efficiency of Cloning and Proliferative Activity of Bone Marrow Multipotent Stromal Cells and Reduce the Content of Osteogenic Multipotent Stromal Cells in CBA Mice. Bull. Exp. Biol. Med. 2017;163(3):356-360.

    Article  CAS  PubMed  Google Scholar 

  5. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J. Cell. Biochem. 2006;98(5):1076-1084.

    Article  CAS  PubMed  Google Scholar 

  6. Kishimoto T, Kaneko T, Ukai T, Yokoyama M, Ayon Haro R, Yoshinaga Y, Yoshimura A, Hara Y. Peptidoglycan and lipopolysaccharide synergistically enhance bone resorption and osteoclastogenesis. J. Periodontal Res. 2012;47(4):646-654.

    Article  CAS  Google Scholar 

  7. Najar M, Krayem M, Meuleman N, Bron D, Lagneaux L. Mesenchymal stromal cells and toll-like receptor priming: a critical review. Immune Netw. 2017;17(2):89-102.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Pevsner-Fischer M, Morad V, Cohen-Sfady M, Rousso-Noori L, Zanin-Zhorov A, Cohen S, Cohen IR, Zipori D. Toll-like receptors and their ligands control mesenchymal stem cells function. Blood. 2007;109(4):1422-1432.

    Article  CAS  PubMed  Google Scholar 

  9. Tukhvatulin AI, Gitlin II, Shcheblyakov DV, Artemicheva NM, Burdelya LG, Shmarov MM, Naroditsky BS, Gudkov AV, Gintsburg AL, Logunov DY. Combined stimulation of Toll-like receptor 5 and NOD1 strongly potentiates activity of NF-κB, resulting in enhanced innate immune reactions and resistance to Salmonella enterica serovar Typhimurium infection. Infect. Immun. 2013;8(10):3855-3864.

    Article  CAS  Google Scholar 

  10. van Heel DA, Ghosh S, Butler M, Hunt K, Foxwell BM, Mengin-Lecreulx D, Playford RJ. Synergistic enhancement of Toll-like receptor responses by NOD1 activation. Eur. J. Immunol;35(8):2471-2476.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yu. F. Gorskaya.

Additional information

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 166, No. 10, pp. 465-469, October, 2018

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gorskaya, Y.F., Tukhvatulin, A.I., Dzharullaeva, A.S. et al. 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. Bull Exp Biol Med 166, 473–476 (2019). https://doi.org/10.1007/s10517-019-04375-6

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-019-04375-6

Key Words

Navigation