Interleukin-1β induces interleukin-6 production through the production of prostaglandin E2 in human osteoblasts, MG-63 cells

This study was conducted to investigate the mechanism of interleukin-1 beta (IL-1 beta)-induced IL-6 production in human osteoblasts (MG-63 cells), Stimulation with IL-1 beta resulted in the production of IL-6 and prostaglandin E-2 (PGE(2)), IL-6 production gradually increased and peaked 96 h after stimulation. IL-6 mRNA was detected between 4 and 72 h after IL-1 beta stimulation. The patterns of PGE(2) 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 PGE(2). Anti-PGE(2) antibody markedly reduced the production of IL-8, In addition, stimulation with 17-phenyl-PGE(2), a PGE receptor-1 (EP-1 receptor) agonist, led to the expression of IL-6 mRNA after pretreatment with IL-1 beta, These findings indicate that IL-1 beta-induced IL-8 production in MG-83 cells involves the following sequence of steps: IL-1 beta-induced COX-2 activation, PGE(2) production, and EP-1 receptor signaling prior to IL-6 production.