RANKL Induces IL-18 Binding Protein Expression in RAW264.7 Cells

The receptor activator of NF-κB (RANK) ligand (RANKL) is a cytokine that is essential for osteoclast development, whereas interleukin (IL)-18 suppresses osteoclastogenesis by increasing granulocyte-macrophage colony-stimulating factor (GM-CSF) production in T-cells. In the present study, we examined the effect of RANKL on the expression of IL-18 and IL-18 binding protein (IL-18BP), a natural inhibitor of IL-18, in RAW264.7 cells. We also examined the effect of conditioned medium derived from RAW264.7 cells on IL-18-induced GM-CSF expression in CD4+ T cells isolated from the spleens of C57BL/6J mice. mRNA expression of IL-18 was significantly suppressed, whereas that of IL-18BP was significantly increased in RANKL-treated RAW264.7 cells compared with untreated cells. RANKL also increased the expression of IL-18BP protein in culture supernatants of RAW264.7 cells. GM-CSF protein expression in CD4+ T-cells stimulated with IL-18 was suppressed by the addition of conditioned medium derived from RANKL-treated RAW264.7 cells. These results suggest that RANKL suppresses the stimulatory effect of IL-18 on GM-CSF expression in CD4+ T-cells via enhancing the production of IL-18BP in RAW264.7 cells.