Inhibition of LPS- and CpG DNA-induced TNF- response by oxidized phospholipids

Physiol 286: L808–L816, 2004. First published November 26, 2003; 10.1152/ajplung.00220.2003.—Lipid oxidation is commonly seen in the innate immune response, in which reactive oxygen intermediates are generated to kill pathogenic microorganisms. Although oxidation products of phospholipids have generally been regarded to play a role in a number of chronic inflammatory processes, several studies have shown that oxidized phospholipids inhibit the LPS-induced acute proinflammatory response in cultured macrophages and endothelial cells. We report in this study that oxidized 1-palmitoyl-2-arachido-noyl-sn-glycero-3-phosphorylcholine (PAPC), but not nonoxidized PAPC, significantly inhibits the LPS-induced TNF- response in intact mice. Oxidized PAPC also inhibits the 2-deoxyribo(cytidine-phosphate-guanosine) (CpG) DNA-induced TNF- response in cul-tured macrophages and intact mice. To elucidate the mechanisms of action, we show that oxidized PAPC, but not nonoxidized PAPC