lysophosphatidylcholine posttranscriptionally inhibits interferon-gamma-induced IP-10, MiG and I-Tac expression in endothelial cells

Objective: Lysophosphatidylcholine (lysoPC) is abundant in atherosclerotic lesions and has potential immunomodulatory activities. This study is aimed to investigate effects of lysoPC on the interferon (IFN)-gamma-induced gene expression, focusing on T cell-directed CXC chemokines relevant to atherosclerosis. Methods and Results: Effects of lysoPC on the IFNgamma-induced gene expression of IFN-inducible protein of 10 kDa (IP-10), IFN-inducible T cell alpha chemoattractant (I-Tac), and monokine induced by IFNgamma (Mig) were evaluated in cultured endothelial cells. Northern blotting showed that lysoPC transiently and dose-dependently inhibited the IFNgamma-induced accumulation of IP-10, Mig and I-Tac but not p48, interferon regulatory factor-1 and guanidine binding protein-1. Nuclear run-off assays showed that lysoPC did not inhibit IP-10, Mig and I-Tac gene transcription. An analysis of the degradation of IP-10, Mig and I-Tac mRNA revealed it to be enhanced by lysoPC. Conclusion: LysoPC selectively inhibits IFNgamma-induced IP-10, I-Tac and Mig expression in endothelial cells, at least in part, by reducing mRNA stability. Thus, lysoPC might regulate T cell-mediated immunity by affecting IFN-1-mediated activation of endothelial cells in atherosclerotic lesions. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.