Recombinant interleukin-1 (IL-1) stimulates prostaglandin E2 production by osteoblastic cells: role of calcium, calmodulin, and cAMP.

Interleukin-1 (IL-1) has been previously shown to stimulate prostaglandin E2 (PGE2) production by osteoblastic cells. This IL-1 effect has also been shown to be potentiated by parathyroid hormone (PTH), which activates both the calcium and the cAMP signal transduction pathways in osteoblastic cells. In the present study, the role of calcium, calmodulin, and cAMP in potentiating the IL-1 effect was examined. The calcium channel blocker verapamil (100 microM) completely inhibited the IL-1 effect. Similarly, the calmodulin antagonist W-7 (50 microM) inhibited the IL-1-induced stimulation. Conversely, the calcium ionophore A23187 (0.1 microM) potentiated the IL-1 effect. The phosphodiesterase inhibitor isobutyl-methylxanthine (IBMX; 100 microM), which elevates cAMP levels in the cells, had a strong potentiating effect on the IL-1-induced PGE2 production. These results suggest that both the calcium and the cAMP second messenger systems can modulate the IL-1 effect on osteoblastic cells.