Effects of interleukin-1, tumor necrosis factor-β, and forskolin on tissue plasminogen activator activity in human osteoblastic osteosarcoma cells

The effects of interleukin-1 (IL-1), forskolin, and tumor necrosis factor β (TNF-β) on tissue plasminogen activator (t-PA) activity were studied in the human osteoblastic osteosarcoma cell line, G292. t-PA activity was measured in the cell media using the chromogenic substrate, S-2251. After a 24 hour incubation period, IL-1 increased t-PA in a dose-dependent manner. The effect of IL-1 at 10.0 U/ml was partially inhibited in the presence of indomethacin. Forskolin (1.0 μM) increased t-PA activity after 24 hours with the effects of combined treatment of IL-1 (1.0 U/ml, 10.0 U/ml) and forskolin being apparently additive in nature. TNF-β (10^-8-10^-7 M) also produced increased t-PA activity in the cell medial after a 24 hour incubation period. These results suggest that the cytokines, IL-1 and TNF-β, can increase t-PA activity in G292 cells and that there is both a cAMP-dependent as well as a cAMP-independent pathway involved in the regulation of this osteoblastic cell function.