Failure to Activate Cytosolic Phospholipase A2 Causes TNF Resistance in Human Leukemic Cells

摘要: Activation of cytosolic phospholipase A2 (cPLA2) by TNF has been shown to be an important component the signaling pathway leading cell death. The role cPLA2 in cytotoxic action was investigated a panel human leukemic lines. could activate only U937 and HL60 TNF-sensitive cells, but not KG1a, CEM, CEM/VLB100 cells that are relatively resistant TNF. Pretreatment with 4-bromophenacyl bromide, inhibitor, rendered lines effect Immunoblot reverse-transcriptase PCR demonstrated expression detectable at both transcriptional translational levels all studied, although CEM expressed mRNA protein lower levels. synthesis cycloheximide, increased TNF-induced activity cytotoxicity Low KG1a line activated activator mellitin, or calcium ionophore A23187. data suggest is involved cells. Resistance may involve either inhibitors act upstream TNF-signaling constitutive defects itself, possibly involving utilization.