Inhibition by glucocorticoids of tumor necrosis factor-mediated cytotoxicityEvidence against lipocortin involvement (original) (raw)

The role of the phospholipase inhibitor proteins, lipocortin-I and -11, in tumor necrosis factor (TNF)-mediated cytotoxicity against L929 fibrosarcoma cells was investigated. We previously reported that TNF-mediated cytotoxicity was inhibited by dexamethasone (DEX), suggesting an involvement of lipocortins [l]. Now we show that, despite inhibition by DEX of TNF-induced arachidonic acid release, DEX has no effect on the synthesis of these lipocortins. Moreover, TNF itself has no effect on the synthesis and phosphorylation of lipocortin-I and -11. Also there was no difference in expression levels of lipocortin-I and -11 between TNF-sensitive and -resistant cells. These data strongly suggest that the protective effect of DEX and other glucocorticoids is not mediated by lipocortins.