Abstract
Hypercholesterolemia is reported to be associated with a T helper (Th) 1 to Th2 switch in apoE-deficient mice. To explore the underlying mechanisms of such immune modulation, we investigated if lysophosphatidylcholine (Lyso-PC), enriched in oxidized LDL, affects cytokine-induced expression of Th1 cell-specific CXC chemokines, IFN-inducible protein of 10 kDa (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T cell a chemoattractant (1-TAC) in cultured endothelial cells. Lyso-PC inhibited IFN-gamma or IFN-gamma plus TNF-alpha-induced IP-10, Mig, and I-TAC mRNA expression but not that of the IRF-1 or IRF-1 dependent molecule, GBP. It also inhibited IP-10 protein secretion in conditioned media induced by IFN-gamma or IFN-y plus TNF-alpha Western analysis demonstrated that Lyso-PC inhibited IFN-gamma-induced STAT-1alpha protein expression, but not that of IRF-1. These results suggest that Lyso-PC selectively inhibits IP-10, Mig, and I-TAC expression through IRF-1-independent mechanisms. This inhibitory effect of Lyso-PC may be involved in the immune modulation by hypercholesterolemia.
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