Lysophosphatidylcholine exhibits selective cytotoxicity, accompanied by ROS formation, in RAW 264.7 macrophages.
Lysophosphatidylcholine (lysoPtdCho) is a component of oxidized low density lipoprotein, and is involved in the pathogenesis of atherosclerosis and inflammation. We studied the effects of lysoPtdCho on cytotoxicity, reactive oxygen species (ROS) production, activation of the extracellular signal-regulated kinase (ERK), mitogen-activated protein kinases and pro-inflammatory gene expression in RAW 264.7 murine macrophage cells. When cells were exposed to lysoPtdCho with various acyl chains in a culture medium containing 10% fetal bovine serum, only 1-linoleoyl (C18:2) lysoPtdCho showed a remarkable cytotoxicity, reaching the highest level at 24 h, and elicited ROS production, suggesting that oxidative stress might be implicated in the cytotoxicity of 1-linoleoyl (C18:2) lysoPtdCho. Presumably in support of this, antioxidants such as magnolol or trolox prevented 1-linoleoyl (C18:2) lysoPtdCho-induced cytotoxicity as well as ROS production, although only partially. Furthermore, the phosphorylation of ERK 1/2 and the expression of pro-inflammatory cytokines such as IL-1beta, CCL2 and CCL5 were augmented by 1-linoleoyl (C18:2) lysoPtdCho. Meanwhile, there was no structural importance of the acyl chain for the cytotoxic action of lysoPtdCho during 10 min incubation in serum-free media. Taken together, it is suggested that in a serum-containing medium, 1-linoleoyl (C18:2) lysoPtdCho can cause a significant cytotoxicity through ROS production, probably accompanied by activation of ERK and induction of related inflammatory cytokines, in RAW 264.7 cells.
Park
Cheon Ho
CH
College of Pharmacy, Chungnam National University, Gung-Dong 220, Yuseong-ku, Taejon 305-764, Republic of Korea.
Kim
Mee Ree
MR
Han
Jong-Min
JM
Jeong
Tae-Sook
TS
Sok
Dai-Eun
DE
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D007249:Inflammation; D008041:Linoleic Acids; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
D016207:Cytokines; D008041:Linoleic Acids; D008244:Lysophosphatidylcholines; D017382:Reactive Oxygen Species; D048052:Mitogen-Activated Protein Kinase 3