Combined Administration of TLR4 (LPS) and TLR3 (Poly I:C) Ligands to CBA Mice Elevates the Content of Osteogenic MSC by 1.6 Times and Increases Content of Bone Marrow MSC to Intermediate Level between Values Attained by Their Individual Administration

Bull Exp Biol Med. 2020 Apr;168(6):767-772. doi: 10.1007/s10517-020-04798-6. Epub 2020 Apr 23.

Abstract

In 1 and 24 h after combined administration of TLR4 (LPS) and TLR3 (Poly I:C) ligands to CBA mice, the content of MSC in bone marrow increased to intermediate value between the levels attained by their individual injections. The content of osteogenic MSC assessed in 24 h postinjection corresponded to the control level in Poly I:C group, decreased in LPS group by 2.5 times relatively to the control, and increased by 1.6 times (relatively to control) after combined administration of the ligands. In 3 h after combined addition of LPS and Poly I:C in vitro to 12-day-old primary culture of mouse bone marrow stromal cells, the concentration of TNFα in culture medium was intermediate between the levels attained by their individual application. The data revealed dependence of activation of stromal tissue on intensity of innate immunity reactions; they also attested to marked elevation of osteogenicity of MSC pool after costimulation with Poly I:C and LPS, which can underlie augmented calcification of the tissues during combined viral and bacterial infections.

Keywords: LPS; Poly (I:C); TLR3 and TLR4 costimulation; mice; multipotent stromal cells (MSC).

MeSH terms

  • Animals
  • Cell Count
  • Cell Differentiation / drug effects
  • Drug Synergism
  • Gene Expression
  • Immunity, Innate / drug effects
  • Injections, Intraperitoneal
  • Interleukin-10 / agonists
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Lipopolysaccharides / pharmacology*
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / immunology
  • Mice
  • Mice, Inbred CBA
  • Osteogenesis / drug effects
  • Osteogenesis / genetics
  • Osteogenesis / immunology
  • Poly I-C / pharmacology*
  • Toll-Like Receptor 3 / agonists
  • Toll-Like Receptor 3 / genetics*
  • Toll-Like Receptor 3 / immunology
  • Toll-Like Receptor 4 / agonists
  • Toll-Like Receptor 4 / genetics*
  • Toll-Like Receptor 4 / immunology
  • Tumor Necrosis Factor-alpha / agonists
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • IL10 protein, mouse
  • Lipopolysaccharides
  • TLR3 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 3
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Poly I-C