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Cardiovascular Research 2005 65(1):263-271; doi:10.1016/j.cardiores.2004.09.017
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Copyright © 2004, European Society of Cardiology

Lysophosphatidylcholine posttranscriptionally inhibits interferon-{gamma}-induced IP-10, Mig and I-Tac expression in endothelial cells

Abdullah Md Sheikha, Hiroshi Ochia,*, Atsushi Manabeb and Junichi Masudaa

aDepartment of Laboratory Medicine, School of Medicine, Shimane University, 89-1 Enya-cho, Izumo, 693-8501, Japan
bDepartment of Obstetrics and Gynecology, School of Medicine, Shimane University, Izumo, Japan

* Corrresponding author. Tel.: +81 853 20 2306; fax: +81 853 20 2310. Email address: hirokana{at}med.shimane-u.ac.jp

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 IFN{gamma}-induced gene expression of IFN-inducible protein of 10 kDa (IP-10), IFN-inducible T cell {alpha} chemoattractant (I-Tac), and monokine induced by IFN{gamma} (Mig) were evaluated in cultured endothelial cells. Northern blotting showed that lysoPC transiently and dose-dependently inhibited the IFN{gamma}-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 IFN{gamma}-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{gamma}-mediated activation of endothelial cells in atherosclerotic lesions.

KEYWORDS IP_10; Interferon-{gamma}; Lysophosphatidylcholine; Endothelial cells; mRNA stability

Time for primary review 26 days


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