Lysophosphatidylcholine inhibits T cell-specific CXC chemokines IP-10, MIG, and I-TAC expression induced by IFN-gamma in human endothelial cells.
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.
Sheikh
A M
AM
Department of Laboratory Medicine, Shimane Medical University, Izumo, Shimane, Japan.
Ochi
H
H
Masuda
J
J
D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D008244:Lysophosphatidylcholines; D007371:Interferon-gamma