[The cytotoxic mechanism of tumor necrosis factor (TNF) in human osteosarcoma cell line TE85--(1). Implication of phospholipase A2 activity in cytotoxicity].
The cytotoxic mechanism of recombinant human tumor necrosis factor (TNF) in human osteosarcoma cells (TE85) was studied from the point of view of phospholipid metabolism. The TNF-induced cytotoxicity, determined by using the dye uptake method, was dose-dependent in the range of 100-10,000 U/ml. Phospholipid metabolism was analyzed in the cells labelled with [3H] arachidonic acid or [3H] glycerol. TNF stimulated the release of arachidonic acid and its metabolites from the cells in a dose-dependent manner. After TNF stimulation, the level of phosphatidylcholine (PC) decreased. Concomitantly, phospholipase A2 (PLA2) hydrolyzed PC producing a transiently increased level of lysophosphatidylcholine. ONO-RS-082, a potent PLA2 inhibitor, reduced the TNF-induced cytotoxicity and the release of arachidonic acid. These observations suggest that PLA2 may play a role in the cytotoxic effect of TNF on human osteosarcoma cells.
Hori
H
H
Department of Orthopaedic Surgery, Gifu University, School of Medicine, Japan.
Takeuchi
S
S
Matsunaga
T
T
Nakashima
S
S
Nozawa
Y
Y
D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D012516:Osteosarcoma / Q000503:physiopathology*; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D010741:Phospholipases A; D054467:Phospholipases A2