Inhibition by glucocorticoids of tumor necrosis factor‐mediated cytotoxicity

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Abstract
The role of the phospholipase inhibitor proteins, lipocortin‐I and ‐II, 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 [1]. 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 ‐II. Also there was no difference in expression levels of lipocortin‐I and ‐II between TNF‐sensitive and ‐resistant cells. These data strongly suggest that the protective effect of DEX and other glucocorticoids is not mediated by lipocortins.