Induction of colony-stimulating factor expression following Staphylococcusor Salmonella interaction with mouse or human osteoblasts

Staphylococcus aureus and Salmonella spp. are common causes of bone disease s; however, the immune response during such infections is not well understo od. Colony-stimulating factors (CSF) have a profound influence on osteoclas togenesis, as well as the development of immune responses following infecti on. Therefore, we questioned whether interaction of osteoblasts with two ve ry different bacterial pathogens could affect CSF expression by these cells . Cultured mouse and human osteoblasts were exposed to various numbers of S . aureus or Salmonella dublin bacteria, and a comprehensive analysis of gra nulocyte-macrophage (GM)-CSF, granulocyte (G)-CSF, macrophage (M)-CSF, and interleukin-3 (IL-3) mRNA expression and cytokine secretion was performed. Expression of M-CSF and IL-3 mRNAs by mouse osteoblasts was constitutive an d did not increase significantly following bacterial exposure. In contrast, GM-CSF and G-CSF mRNA expression by mouse osteoblasts was dramatically upr egulated following interaction with either viable S. aureus or Salmonella. This increased mRNA expression also translated into high levels of GM-CSF a nd G-CSF secretion by mouse and human osteoblasts following bacterial expos ure. Viable S. aureus and Salmonella induced maximal levels of CSF mRNA exp ression and cytokine secretion compared to W-killed bacteria. Furthermore, GR;I-CSF and G-CSF mRNA expression could be induced in unexposed osteoblast s separated by a permeable Transwell membrane from bacterially exposed oste oblasts. M-CSF secretion was increased in cultures of exposed human osteobl asts but not in exposed mouse osteoblast cultures. Together, these studies are the first to define CSF expression and suggest that, following bacteria l exposure, osteoblasts may influence osteoclastogenesis, as well as the de velopment of an immune response, via the production of these cytokines.