IL-1-INDUCED MURINE OSTEOBLAST IL-6 PRODUCTION IS MEDIATED BY THE TYPE-1 IL-1 RECEPTOR AND IS INCREASED BY 1,25 DIHYDROXYVITAMIN-D(3)

IL-1-induced osteoblast IL-6 production represents one possible mechan ism by which IL-1 augments bone resorption. In this report, we show th at the murine osteoblastic cell line (MC3T3-E1) expresses type 1 IL-1 receptors based on I-125-HrIL1alpha binding, blocked by type 1 IL-1R a ntibodies (35F5), and analysis of MC3T3 RNA by reverse transcription ( RT)-DNA amplification and Northern analysis. MC3T3 cells do not expres s detectable type 2 IL-1R mRNA by RT-DNA amplification. IL-1 induces ( IL-1 ED50, 0.1 pM) IL-6 production through the type 1 IL-1R as 35F5 an tibodies block IL-1-stimulated IL-6 production. Vitamin D3 increases I L-1R expression dose- and metabolite-dependently, with 1,25-(OH)2D3 ha ving the greatest potency, and also enhances IL-1's capacity to stimul ate IL-6 production at low IL-1 levels. Both IL-1 and 1,25-(OH)2D3 ind uce type 1 IL-1R and not type 2 IL-1R upregulation based on ligand bin ding and RT-DNA amplification. Increased IL-1R expression requires a 5 -7-h treatment and is protein/RNA synthesis dependent. These observati ons imply that IL-1-induced IL-6 production in osteoblasts is mediated by type 1 IL-1Rs and that increased IL-1R expression could play a rol e in mediating IL-1-induced skeletal responses.