Oxidized
phospholipids, such as the products of the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by nonenzymatic radical attack, are known to be formed in a number of inflammatory diseases. Interest in the bioactivity and signaling functions of these compounds has increased enormously, with many studies using cultured immortalized and primary cells, tissues, and animals to understand their roles in disease pathology. Initially, oxidized
phospholipids were viewed largely as culprits, in line with observations that they have proinflammatory effects, enhancing inflammatory
cytokine production, cell adhesion and migration, proliferation, apoptosis, and
necrosis, especially in vascular endothelial cells, macrophages, and smooth muscle cells. However, evidence has emerged that these compounds also have protective effects in some situations and cell types; a notable example is their ability to interfere with signaling by certain
Toll-like receptors (TLRs) induced by microbial products that normally leads to
inflammation. They also have protective effects via the stimulation of
small GTPases and induce up-regulation of
antioxidant enzymes and cytoskeletal rearrangements that improve endothelial barrier function. Oxidized
phospholipids interact with several cellular receptors, including
scavenger receptors,
platelet-activating factor receptors, peroxisome proliferator-activated receptors, and TLRs. The various and sometimes contradictory effects that have been observed for oxidized
phospholipids depend on their concentration, their specific structure, and the cell type investigated. Nevertheless, the underlying molecular mechanisms by which oxidized
phospholipids exert their effects in various pathologies are similar. Although our understanding of the actions and mechanisms of these mediators has advanced substantially, many questions do remain about their precise interactions with components of cell signaling pathways.