Expression of cytokines IL-4, IL-12, IL-15, IL-18, and IFNγ and modulation by different growth factors in cultured human osteoblast-like cells

Abstract

The antigenic phenotype of cultured human osteoblast-like cells, their ability to phagocytose particles of different nature and size, and their capacity to stimulate allogeneic T cells suggest that they are related to other cell populations with which they may also have immunological functions in common. The objective of this study was to investigate the intracytoplasmatic presence of cytokines and their modulation by different biomolecules. Immunocytochemistry and flow cytometry were used to study the expression of IL-4, IL-12, IL-15, IL-18, and IFNgamma cytokines. To investigate whether FGF, TGF, PDGF, IL-1, and IFNgamma modulate expression of these cytokines in cultured human osteoblast-like cells we used flow cytometry. IL-4, IL-12, IL-15, IL-18, and IFNgamma cytokines were expressed by all the cultured human osteoblast-like cells studied. Treatment with FGF and TGFbeta1 reduced the percentage expression and fluorescence intensity of the cytokines. PDGF treatment enhanced their fluorescence intensity but did not modify their expression. IL-1 treatment produced a small reduction in expression and fluorescence intensity of IL-12 and IL-15, but did not produce major changes in the expression of IL-4, IL-18, or IFNgamma. IFNgamma markedly increased the fluorescence intensity of the cytokines. The results indicate that human osteoblast-like cells may perform immunological functions (e.g., synthesizing cytokines with immune regulator function) that can be modulated by different biomolecules related to bone tissue and/or immune response.

Nitrogen-containing bisphosphonates modulate the antigenic profile and inhibit the maturation and biomineralization potential of osteoblast-like cells

“…This implies major changes in the complex physiology of the osteoblast, which is regulated by multiple local and systemic factors that may regulate the activity of a specific transcription factor [16,19,27]. TGF-β1 is known to play an important role in regulating and stimulating the differentiation of osteoprogenitors during fracture repair [28] and has been described as responsible, among other growth factors, for the biostimulatory effect on osteoblast cells of various treatments [29,30].…”

“…Besides their essential role in bone formation and repair, osteoblasts possess immunological functions, including T lymphocyte stimulation, phagocytic activity, and cytokine synthesis [15][16][17][18][19][20][21][22][23]. Osteoblasts express CD54, CD80, CD86, and HLA-DR surface antigens according to their degree of differentiation and/or activation, and their antigenic profile is modulated by the presence of different cytokines and growth factors [17,18,22].…”

IL-15 promotes osteoclastogenesis via the PLD pathway in rheumatoid arthritis

“…IL-15 is produced in substantial amounts by macrophages and fibroblasts in the rheumatoid synovial membrane [39]. IL-15 stimulates the differentiation of osteoclast progenitors into preosteoclasts, mediate inflammatory bone loss [12,14,40,41] and acts in the early stage of osteoclastogenesis. Thus, IL-15 may play a crucial role in the pathogenesis of RA including osteoclastogenesis, a cause of the joint destruction in RA.…”

Genomic expression of mesenchymal stem cells to altered nanoscale topographies

“…PDGF is involved in cell proliferation and survival (Ruiz et al 2007). Figure S6, electronic supplementary material, shows that, while culture on the 40 : 400 topography results in a small number of downregulations, culture of MSCs on 3% : 3000 results in a broad number of pathway-associated upregulations (figure 2a).…”