EFFECTS OF INTERLEUKIN-1-ALPHA ON ARACHIDONIC-ACID METABOLISM IN HUMAN OSTEOSARCOMA OSTEOBLASTIC CELLS

The effects of interleukin-1alpha, (IL-1alpha) on arachidonic acid (AA ) metabolism were studied in the human osteosarcoma cell lines, G292 a nd SaOS-2. The cells were prelabeled with H-3-arachidonic acid. Radiol abeled metabolites were measured by reversed-phase high-pressure liqui d chromatography with a radioactive detector. Indomethacin inhibited p rostaglandin E2 (PGE2) production without affecting lipoxygenase (LO) products in G292 cells. In the G292 cells, IL-1alpha (50 U/ml) induced a 10-fold increase in PGE2 production at all the incubation times tes ted, and a significant two-fold increase in 5 hydroxyeicosatetraenoic acid (HETE) formation after 48 h. These effects were not seen in SaOS- 2 cells under identical conditions. These results suggest that, althou gh some osteosarcomal cell lines may not respond directly to IL-1 with effects on AA metabolism, the mechanism of its action in others may i nvolve modulation of both cyclooxygenase (CO) and LO pathways.