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.

Lysophosphatidylcholine induces glial cell activation: Role of rho kinase

“…The proinflammatory function of LPC, produced by PLA 2 , is described mainly in relation to atherosclerosis involving endothelial cells, smooth muscle cells, macrophages, and T-cells (Cieslik et al, 1998;Kume and Gimbrone, 1994;Kume et al, 1992;Morimoto et al, 2001;Nishi et al, 1998;Ochi et al, 1995;Oka et al, 2000;Sakata-Kaneko et al, 1998). LPC are also implicated in neurodegenerative disorders which exhibit considerable extents of neuroinflammation including Parkinson's disease, multiple sclerosis, and cerebral ischemia (Andreoli et al, 1973;Kinouchi et al, 1990;Lee et al, 2004).…”

“…Previous reports indicate that LPC has immunomodulatory functions as it induces the expression of multiple genes relevant to inflammation including cytokines and chemokines, adhesion molecules, growth factors and proinflammatory enzymes in endothelial cells, smooth muscle cells, macrophages, and T-cells (Cieslik et al, 1998;Kume and Gimbrone, 1994;Kume et al, 1992;Morimoto et al, 2001;Nishi et al, 1998;Ochi et al, 1995;Oka et al, 2000;Sakata-Kaneko et al, 1998). LPC is also reported to inhibit expression of some genes in inflammatory responses including interferon g (IFNg)-induced Th1-cell-specific chemokines such as IFNg-inducible protein (10 kDa), monokine induced by IFNg and IFN-induced T-cella chemoattractant (Sheikh et al, 2005).…”

Krabbe disease: psychosine-mediated activation of phospholipase A2 in oligodendrocyte cell death

“…These recruited macrophages further upregulate the inflammatory disease and participate in the progressive demyelinating disease process in Krabbe disease and in twitcher mice. LPC is known to act as a chemoattractant for monocytes (55) and T lymphocytes (56,57) and also enhances the production of interferon-g by activated T cells, thus promoting an inflammatory reaction (58,59). Because elevated levels of LPC are observed in Krabbe and twitcher brain, it can be postulated that LPC may, at least in part, be responsible for the inflammatory response observed in Krabbe disease and in twitcher mice.…”

Synthetic Peptide (P-21) Derived from Asp-Hemolysin Inhibits the Induction of Apoptosis on HUVECs by Lysophosphatidylcholine

“…LPC has many effects that are expected to play important roles in atherogenesis. 18) For example, LPC stimulates cytokine, 19) adhesion molecules, 20) growth factor population, 21) and apoptosis induction. 22) Many studies have identified that cell apoptosis increased in atherosclerotic plaques compared with normal vascular vessels.…”