© 1998 American Heart Association, Inc.
Original Contributions |
Lysophosphatidylcholine Enhances Cytokine-Induced Interferon Gamma Expression in Human T Lymphocytes
From the Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Correspondence to Noriaki Kume, MD, PhD, Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606, Japan. E-mail nkume{at}kuhp.kyoto-u.ac.jp
Abstract—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-
) secretion and gene expression in human T
lymphocytes. Lyso-PC–induced upregulation of IFN- 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- mRNA half-lives in human T cells.
Transient transfection of IFN- promoter-reporter gene construct in
the human T-cell line Jurkat cells demonstrated that lyso-PC stimulated
the transcription of IFN- promoter-driven luciferase gene.
Analyses of serial deletion mutations of IFN- promoter
revealed that the lyso-PC–responsive element is located between base
pairs -102 and -78 of the transcription initiation site of the
IFN- gene. Enhanced expression of IFN- in T lymphocytes by
lyso-PC may play a crucial role in atherogenesis.
Key Words: lysophosphatidylcholine • interferon gamma • T lymphocyte • atherosclerosis
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