Lysophosphatidylcholine enhances cytokine-induced interferon gamma expression in human T lymphocytes.
Accumulation of substantial numbers of activated T lymphocytes, as well as monocyte/macrophages, in focal areas of arterial intima appears to be a hallmark of atherogenesis. Our previous report demonstrated that lysophosphatidylcholine (lyso-PC), a polar phospholipid component that is increased in atherogenic lipoproteins and atherosclerotic lesions, can upregulate the expression of heparin-binding epidermal growth factor-like growth factor and the interleukin (IL)-2 receptor in cultured human peripheral T lymphocytes. In this study, we show that lyso-PC can also enhance interferon gamma (IFN-gamma) secretion and gene expression in human T lymphocytes. Lyso-PC-induced upregulation of IFN-gamma depended on the presence of IL-2, IL-12, or phytohemagglutinin in culture media and was similarly observed in both CD4+ and CD8+ subsets. Actinomycin D chase by Northern blotting showed that lyso-PC significantly prolonged IFN-gamma mRNA half-lives in human T cells. Transient transfection of IFN-gamma promoter-reporter gene construct in the human T-cell line Jurkat cells demonstrated that lyso-PC stimulated the transcription of IFN-gamma promoter-driven luciferase gene. Analyses of serial deletion mutations of IFN-gamma promoter revealed that the lyso-PC-responsive element is located between base pairs - 102 and -78 of the transcription initiation site of the IFN-gamma gene. Enhanced expression of IFN-gamma in T lymphocytes by lyso-PC may play a crucial role in atherogenesis.
Nishi
E
E
Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, Japan.
Kume
N
N
Ueno
Y
Y
Ochi
H
H
Moriwaki
H
H
Kita
T
T
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional; D012636:Secretory Rate / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic
D016207:Cytokines; D007376:Interleukin-2; D008244:Lysophosphatidylcholines; D010835:Phytohemagglutinins; D018664:Interleukin-12; D007371:Interferon-gamma