Effects of interleukin-1, tumor necrosis factor -beta, and forskolin on tissue plasminogen activator activity in human osteoblastic osteosarcoma cells.
The effects of interleukin-1 (IL-1), forskolin, and tumor necrosis factor beta (TNF-beta) 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 microM) 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-beta (10(-8)-10(-7)M) also produced increased t-PA activity in the cell media after a 24 hour incubation period. These results suggest that the cytokines, IL-1 and TNF-beta, 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.
Kohl
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AC
Department of Oral Biology, School of Dental Medicine, State University of New York, Buffalo 14214.
Tatakis
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DN
Hansen
C
C
Dziak
R
R
D005576:Colforsin / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D007375:Interleukin-1; D008233:Lymphotoxin-alpha; D005576:Colforsin; D010959:Tissue Plasminogen Activator; D007213:Indomethacin