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 Feb;158(4):465-70. doi: 10.1007/s10517-015-2786-z. Epub 2015 Feb 24.

Abstract

The content of multipotent stromal cells (MSC) in the bone marrow and efficiency of their cloning (ECF-MSC) increased by 3 times 1 day after administration of complex S. typhimurium antigens to CBA mice, while the relative content of alkaline phosphatase-positive MSC colonies (marker of osteogenesis; P(+) colonies) decreased from 14% (control) to 3%. After administration of the complex S. typhimurium antigens to CBA mice 3 h after (or 3 h before) curettage or treatment with morphogenetic protein (BMP-2), the content of MSC and ECF-MSC decreased on the next day by ~3 times in comparison with animals receiving antigens alone and approached the control level. The relative content of P(+) colonies increased to 20 and 35%, respectively, in comparison with animals receiving antigens (3%), but was significantly lower than after curettage (34%) or BMP-2 (42%) administration. Expression of IL-1β, IL-6, IL-12, TNF-α, and IFN-γ genes in the primary cultures of stromal bone marrow cells induced by antigen administration was suppressed, while the concentrations of IL-12 and TNF-α in the culture medium sharply decreased after antigen treatment in combination with curettage or BMP-2 administration. Administration of complex S. typhimurium antigens after pretreatment with BMP-2 (3 h before) was associated with a decrease in serum levels of IL-2, IFN-γ, IL-12, and TNF-α in mice receiving BMP-2+S. typhimurium group 4 h after treatment in comparison with the animals receiving only S. typhimurium antigens alone by 1.9, 4.4, 1.5, and 6 times, respectively, i.e. to normal level or below it, while the concentration of IL-10 increased by almost 2 times, which probably reflected anti-inflammatory properties of BMP-2. These data probably attest to competitive relations between osteogenesis and immune response at the level of MSC.

MeSH terms

  • Animals
  • Antigens, Bacterial / pharmacology*
  • Bone Marrow Cells / drug effects*
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Curettage
  • Cytokines / blood*
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Interleukin-2 / blood
  • Mice
  • Mice, Inbred CBA
  • Osteogenesis / drug effects*
  • Salmonella typhimurium / immunology*
  • Stromal Cells / drug effects*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Antigens, Bacterial
  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Cytokines
  • Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma