LYSOPHOSPHATIDYLCHOLINE ENHANCES CYTOKINE-INDUCED INTERFERON-GAMMA EXPRESSION IN HUMAN T-LYMPHOCYTES

Accumulation of substantial numbers of activated T lymphocytes, as wel l as monocyte/macrophages, in focal areas of arterial intima appears t o be a hallmark of atherogenesis. Our previous report demonstrated tha t lysophosphatidylcholine (lyso-PC), a polar phospholipid component th at is increased in atherogenic lipoproteins and atherosclerotic lesion s, can upregulate the expression of heparin-binding epidermal growth f actor-like growth factor and the interleukin (IL)-2 receptor in cultur ed human peripheral T lymphocytes. In this study, we show that lyso-PC can also enhance interferon gamma (IFN-gamma) secretion and gene expr ession in human T lymphocytes. Lyse-PC-induced upregulation of IFN-gam ma depended on the presence of IL-2, IL-12, or phytohemagglutinin in c ulture media and was similarly observed in both CD4(+) and CD8(+) subs ets. Actinomycin D chase by Northern blotting showed that lyse-PC sign ificantly prolonged IFN-gamma mRNA half-lives in human T cells. Transi ent transfection of IFN-gamma promoter-reporter gene construct in the human T-cell line Jurkat cells demonstrated that lyse-PC stimulated th e 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 e xpression of IFN-gamma in T lymphocytes by lyso-PC may play a crucial role in atherogenesis.