Modulation of tumor necrosis factor-alpha cytotoxicity in L929 cells by bacterial toxins, hydrocortisone and inhibitors of arachidonic acid metabolism.
L929 cells were incubated with tumor necrosis factor-alpha (TNF-alpha) in the presence or absence of various inhibitors of arachidonic acid metabolism. The addition of either hydrocortisone or nordihydroguaiaretic acid (NDGA) decreased the cytotoxic effect of TNF-alpha but exogenously added arachidonate or linoleate, indomethacin and eicosatetraynoic acid (ETYA) were without effect. While it was found that TNF-alpha stimulated arachidonic acid release, no metabolites of this fatty acid could be evidenced. Cytotoxicity of TNF-alpha could also be decreased by the addition of either cholera or pertussis toxin. These results suggest that a GTP-binding protein is involved in the cytotoxic action of TNF-alpha. Arachidonic acid, released possibly by a phospholipase A2, might also play a role, but probably not via its conversion to known metabolites.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001427:Bacterial Toxins / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology; D006854:Hydrocortisone / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D010741:Phospholipases A / Q000502:physiology; D054467:Phospholipases A2; D012709:Serum Albumin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D001095:Arachidonic Acids; D001427:Bacterial Toxins; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins; D006854:Hydrocortisone; D007213:Indomethacin