Lysophosphatidylcholine up-regulates CXCR4 chemokine receptor expression in human CD4 T cells

Abstract: Oxidized low-density lipoprotein (OxLDL) is an inflammatory modulator in the atheroscle-rotic plaque. We examined the effect of lysophos-phatidylcholine (lysoPC), a main phospholipid component of OxLDL, on inflammatory responses in human CD4 T cells. We found that lysoPC dose-and time-dependently increased expression of CXCR4, the chemokine receptor on CD4 T cells. This increase was inhibited by caffeic acid phen-ethyl ester or SN50, nuclear factor-B inhibitors, and also by suppression of G2A expression, the specific receptor for lysoPC, using antisense oligo-nucleotide. lysoPC enhanced CD4 T cell chemo-taxis in response to stromal cell-derived factor-1 (SDF-1), the exclusive ligand for CXCR4. lysoPC also enhanced SDF-1-stimulated production of inflammatory cytokines interleukin-2 and inter-feron- by CD4 T cells activated by anti-CD3 immunoglobulin G. In conclusion, this study demonstrates that lysoPC directly modulates in-flammatory responses in human CD4 T cells. The data suggest that the presence of lysoPC and SDF-1 in atherosclerotic lesions may trigger in-flammatory responses mediated by CD4 T cells, which may play an important role in progression o