Lysophosphatidylcholine enhances cytokine-induced interferon gamma expression in human T lymphocytes.

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-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.

• Authors: E Nishi, N Kume, Y Ueno, H Ochi, H Moriwaki, T Kita
• Journal: Circulation research (Circ Res) Vol. 83 Issue 5 Pg. 508-15 (Sep 07 1998) ISSN: 0009-7330 [Print] United States
• PMID: 9734473 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Interleukin-2
• Lysophosphatidylcholines
• Phytohemagglutinins
• Interleukin-12
• Interferon-gamma

Topics

• CD4-Positive T-Lymphocytes (drug effects, metabolism)
• CD8-Positive T-Lymphocytes (drug effects, metabolism)
• Cells, Cultured
• Cytokines (pharmacology)
• Gene Expression
• Humans
• Interferon-gamma (biosynthesis, genetics, physiology)
• Interleukin-12 (pharmacology)
• Interleukin-2 (pharmacology)
• Lysophosphatidylcholines (pharmacology)
• Phytohemagglutinins (pharmacology)
• RNA Processing, Post-Transcriptional
• Secretory Rate (drug effects)
• T-Lymphocytes (drug effects, immunology, metabolism)
• Transcription, Genetic