JNK1/c-Jun and p38α MAPK/ATF-2 pathways are responsible for upregulation of Fas/FasL in human chronic myeloid leukemia K562 cells upon exposure to Taiwan cobra phospholipase A₂

Fas and FasL expression upregulation was found in human leukemia K562 cells upon exposure to Naja naja atra phospholipase A₂ (PLA₂). PLA₂ treatment induced an increase in intracellular Ca²⁺ ([Ca²⁺]i) and ROS generation levels, leading to activation of p38 MAPK and JNK. Suppression of both p38 MAPK and JNK abrogated Fas and FasL upregulation. Unlike PLA₂, catalytically inactive PLA₂ treatment did not markedly increase Fas and FasL protein expression, and p38 MAPK activation was exclusively responsible for catalytically inactive PLA ₂-induced increase in Fas and FasL protein expression. Knockdown of p38α MAPK and JNK1 by siRNA proved that p38α MAPK and JNK1 were involved in ATF-2 and c-Jun phosphorylation, respectively. Compared with the p38α MAPK/ATF-2 pathway, the JNK1/c-Jun pathway played a crucial role in Fas/FasL upregulation. Unlike arachidonic acid, lysophosphatidylcholine mimicked the PLA₂ action in inducing Fas/FasL upregulation. Together with the previous finding that c-Jun and ATF-2 are involved in transcriptional regulation of Fas and FasL, our data suggest that PLA₂ induces Fas and FasL upregulation through p38a MAPK/ATF-2 and JNK1/c-Jun pathways in K562 cells, and PLA₂ catalytic activity is involved in this action.