Aim: 

To explore the important of Toll-like Receptors in the responses of cells to oxidized phospholipids. Oxidation products of 1-palmitoyl-2-arachidonoyl-3-glycerophosphocholine (PAPC) are known to mimic the biological effects of oxidized LDL, and consequently there has been much interest in their cellular effects and the mechanisms by which these are achieved. Pro-inflammatory effects such as leukocyte-endothelial adhesion, chemokine production, and induction of signalling pathways to inflammation have been reported. One possible mechanism by which oxidized lipids could induce inflammatory responses involves interaction with the Toll-like receptor (TLRs), which are present on many cells and recognize pathogen associated molecular patterns (PAMPs) in order to detect infection and damage to host tissues.

Methods: 

A wide variety of methods have been used in these studies, including reporter assays with transfected HEK293 cells, western blotting, ELISAs for inflammatory markers, protein binding assays, RT-PCR, and cell viability assays.

Results: 

We have shown that although oxPAPC and its components can induce IL-8 expression in a variety of cells, a classical response involving signalling via NFkB does not occur, and it appears that in most cell types, oxPAPC does not interact with TLRs. Instead, oxPAPC can inhibit the activation of TLRs 2 and 4 by their ligands, and this involves the competitive binding of oxPAPC to the lipid binding proteins LPS-binding protein, CD14 and MD2 that are involved in stimulation of these receptors. This can reduce adverse inflammatory responses in models of infection and septic pathology.

Conclusion: 

Overall it can be concluded that oxidized phospholipids have complex and pleiotrophic biological effects.