Lysophosphatidylcholine up-regulates CXCR4 chemokine receptor expression in human CD4 T cells.
Oxidized low-density lipoprotein (OxLDL) is an inflammatory modulator in the atherosclerotic plaque. We examined the effect of lysophosphatidylcholine (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 phenethyl ester or SN50, nuclear factor-kappaB inhibitors, and also by suppression of G2A expression, the specific receptor for lysoPC, using antisense oligonucleotide. lysoPC enhanced CD4 T cell chemotaxis 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 interferon-gamma by CD4 T cells activated by anti-CD3 immunoglobulin G. In conclusion, this study demonstrates that lysoPC directly modulates inflammatory responses in human CD4 T cells. The data suggest that the presence of lysoPC and SDF-1 in atherosclerotic lesions may trigger inflammatory responses mediated by CD4 T cells, which may play an important role in progression of atherosclerosis.
Han
Ki Hoon
KH
College of Medicine, Asan Medical Center, 388-1 Pungnap-2 dong, Songpa-gu 138-736, Seoul, South Korea.
Hong
Kyung Hee
KH
Ko
Jesang
J
Rhee
Kyong Suk
KS
Hong
Myeong Ki
MK
Kim
Jae Joong
JJ
Kim
You Ho
YH
Park
Seung Jung
SJ
D001161:Arteriosclerosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D054377:Chemokine CXCL12; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000187:drug effects*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
C515255:CXCL12 protein, human; D018797:Cell Cycle Proteins; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; C115270:G2A receptor; D008244:Lysophosphatidylcholines; D016328:NF-kappa B; D019718:Receptors, CXCR4; D043562:Receptors, G-Protein-Coupled