Interleukin-1β Induces Interleukin-6 Production through the Production of Prostaglandin E₂ in Human Osteoblasts, MG-63 Cells

Abstract

This study was conducted to investigate the mechanism of interleukin-1β (IL-1β)-induced IL-6 production in human osteoblasts (MG-63 cells). Stimulation with IL-1β resulted in the production of IL-6 and prostaglandin E₂ (PGE₂). IL-6 production gradually increased and peaked 96 h after stimulation. IL-6 mRNA was detected between 4 and 72 h after IL-1β stimulation. The patterns of PGEZ production and the expression of cyclooxygenase-2 (COX-2) mRNA were biphasic after stimulation. Actinomycin D, cycloheximide, indomethacin, and NS-398 (COX-2 inhibitor) suppressed the production of IL-6 and PGE₂. Anti -PGE₂, antibody markedly reduced the production of IL-6. In addition, stimulation with 17-pbenyl-PGE₂, a PGE receptor-1 (EP-1 receptor) agonist, led to the expression of IL-6 mRNA after pretreatment with IL-1β. These findings indicate that IL-1β-induced IL-6 production in MG-63 cells involves the following sequence of steps: IL-1β-induced COX-2 activation, PGE₂, production, and EP-1 receptor signaling prior to IL-6 production.