title: 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.
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.
authors.affiliation: Laboratory of Immunity Regulation, Laboratory of Bioactive Nanostructures, Laboratory of Microbiology of Latent Infections, N. F. Gamaleya Research Institute of Epidemiology and Microbiology, the Ministry of Health of the Russian Federation, Moscow, Russia, ulia.gorskaya@nearmedic.ru.
authors.forename: Yu F
authors.initials: YF
authors.lastname: Gorskaya
authors.forename: T A
authors.initials: TA
authors.lastname: Danilova
authors.forename: A S
authors.initials: AS
authors.lastname: Karyagina
authors.forename: V G
authors.initials: VG
authors.lastname: Lunin
authors.forename: V I
authors.initials: VI
authors.lastname: Grabko
authors.forename: M S
authors.initials: MS
authors.lastname: Bartov
authors.forename: A V
authors.initials: AV
authors.lastname: Gromov
authors.forename: T M
authors.initials: TM
authors.lastname: Grunina
authors.forename: L A
authors.initials: LA
authors.lastname: Soboleva
authors.forename: I M
authors.initials: IM
authors.lastname: Shapoval
authors.forename: V G
authors.initials: VG
authors.lastname: Nesterenko
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects*; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D003475:Curettage; D016207:Cytokines / Q000097:blood*; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D051379:Mice; D008808:Mice, Inbred CBA; D010012:Osteogenesis / Q000187:drug effects*; D012486:Salmonella typhimurium / Q000276:immunology*; D017154:Stromal Cells / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000942:Antigens, Bacterial; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma