The 70-kDa TNF cell surface receptor (p70TNFR) and the related 75-kDa nerve growth factor (NGF) receptor (p75NGFR) can enhance cell death. Expression of p70TNFR or p75NGFR in HeLa cells resulted in enhanced TNF-induced apoptotic cell death with a corresponding elevation of cytosolic phospholipase A2 (cPLA2) levels. This response was apparent by 24 h, did not occur with NGF treatment or when vector or TrkA NGFR were expressed and was reversed by dexamethasone pretreatment. These findings reveal a novel mechanism by which the p70TNFR and p75NGFR achieve enhanced TNFR-mediated programmed cell death by elevating cPLA2 levels.
