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.


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.


CONCLUSIONS
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.
Sheikh
Abdullah Md
AM
Department of Laboratory Medicine, School of Medicine, Shimane University, 89-1 Enya-cho, Izumo, 693-8501, Japan.
Ochi
Hiroshi
H
Manabe
Atsushi
A
Masuda
Junichi
J
D001161:Arteriosclerosis / Q000276:immunology; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000037:antagonists & inhibitors*; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D018925:Chemokines / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000494:pharmacology*
C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D008244:Lysophosphatidylcholines; D007371:Interferon-gamma