Oxidized Phospholipid Inhibition of LPS-Signaling: a Good Side to the Bad Guys?

As chronic inflammatory processes are now understood to underpin the development of atherosclerosis, and oxidative modification of lipids and lipoproteins has long been considered to play a role in this disease, the mechanisms linking lipid peroxidation with inflammatory signaling are a key area of current atherosclerosis research. Oxidized phospholipids (OxPLs) in particular have received considerable attention in this context since their identification as key mediators of the chemokine-inducing properties of moderately oxidized low-density lipoprotein (mmLDL).1 OxPLs are formed not only during the oxidative modification of LDL, but also within apoptotic cell membranes, and have been shown to accumulate to reach micromolar concentrations in inflamed tissues, such as atheroma.2 To date, it has been widely assumed that OxPLs are predominantly proinflammatory mediators, on the basis of their ability to upregulate expression of interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 and the binding of monocytes to endothelial cells.2 Paradoxically, however, it has also been shown that OxPLs are potent inhibitors of inflammatory signaling induced by bacterial lipopolysaccharide (LPS, endotoxin), considered by immunologists to be a prototypic proinflammatory agent, both in vitro and in vivo.