Inhibition by glucocorticoids of tumor necrosis factor-mediated cytotoxicity. Evidence against lipocortin involvement.
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.
Beyaert
R
R
Laboratory of Molecular Biology, State University of Gent, Belgium.
Suffys
P
P
Van Roy
F
F
Fiers
W
W
D017302:Annexins; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D008715:Methionine / Q000378:metabolism; D010766:Phosphorylation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D017302:Annexins; D001095:Arachidonic Acids; D002135:Calcium-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D003907:Dexamethasone; D008715:Methionine