Inhibition by glucocorticoids of tumor necrosis factor-mediated cytotoxicity. Evidence against lipocortin involvement

FEBS Lett. 1990 Mar 12;262(1):93-6. doi: 10.1016/0014-5793(90)80161-b.

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. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexins
  • Arachidonic Acid
  • Arachidonic Acids / metabolism
  • Calcium-Binding Proteins / physiology*
  • Cell Survival / drug effects
  • Dexamethasone / pharmacology
  • Methionine / metabolism
  • Phosphorylation
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Annexins
  • Arachidonic Acids
  • Calcium-Binding Proteins
  • Tumor Necrosis Factor-alpha
  • Arachidonic Acid
  • Dexamethasone
  • Methionine