RECOMBINANT HUMAN TUMOR-NECROSIS-FACTOR-ALPHA SUPPRESSES SYNTHESIS, ACTIVITY AND SECRETION OF LIPOPROTEIN-LIPASE IN CULTURES OF A HUMAN OSTEOSARCOMA CELL-LINE

The effect of recombinant human tumour necrosis factor-alpha (TNF-alph a) on synthesis, activity and secretion of lipoprotein lipase (LPL) wa s examined using a human osteosarcoma cell line, osteosarcoma Takase ( OST). Treatment of OST cells with TNF-alpha decreased LPL synthesis, r esulting in a decrease in expression of activity and secretion of LPL. When OST cells were incubated with glycerol tri[1-C-14]palmitate, TNF -alpha decreased dose- and time-dependently the production of (CO2)-C- 14 and the amounts of radioactivity incorporated into cellular triacyl glycerol and phospholipid. The similar reduction of synthesis and acti vity of LPL as suppression of CO2 production and cellular lipid synthe sis indicated that the suppression of (CO2)-C-14 production and C-14-l abelled lipid synthesis was secondary. TNF-alpha also suppressed expre ssion of proliferating cell nuclear antigen, indicating that it had an anti-proliferative activity on OST cells. The findings suggest that o ne cause of the anti-proliferative activity of TNF-alpha is the suppre ssion of the LPL-mediated supply of non-esterified fatty acids as an e nergy source for growth.