Lysophosphatidylcholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T lymphocytes.
Atherosclerotic lesions contain substantial numbers of activated T lymphocytes in addition to monocytes/macrophages. T cell-derived cytokines and growth factors may play a role in atherogenesis; however, stimuli responsible for T-cell activation in atherogenesis have not been fully elucidated. In this study, we provide evidence that lysophosphatidylcholine (lyso-PC), a polar phospholipid component increased in atherogenic lipoproteins and atherosclerotic lesions, can upregulate gene expression and secretion of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in cultured T lymphocytes isolated from human peripheral blood. Effects of lyso-PC on T lymphocytes appear to be selective and specific, since lyso-PC also increases interleukin (IL)-2 receptor expression but does not affect mRNA levels for IL-2 or IL-4. Lyso-PC-induced upregulation of HB-EGF and IL-2 receptor mRNA in peripheral T cells is mostly dependent on exogenous IL-2 in conditioned medium. The effect of lyso-PC on HB-EGF induction was more potent in CD4+ cells than in CD8+ cells, although lyso-PC increases IL-2 receptor expression dramatically in both CD4+ cells and CD8+ cells. Lyso-PC similarly increased HB-EGF expression in Jurkat cells, a cell line for human CD4+ T lymphocytes. These results in vitro suggest that lyso-PC may be an important stimulus for T cells in atherogenesis in vivo to upregulate HB-EGF and that T cell-derived smooth muscle growth factors may modulate atherosclerotic progression.
Nishi
E
E
Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Japan.
Kume
N
N
Ochi
H
H
Moriwaki
H
H
Wakatsuki
Y
Y
Higashiyama
S
S
Taniguchi
N
N
Kita
T
T
D001681:Biological Assay; D015152:Blotting, Northern; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000097:blood / Q000235:genetics*; D005434:Flow Cytometry; D006493:Heparin / Q000097:blood / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D015854:Up-Regulation
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008244:Lysophosphatidylcholines; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D004815:Epidermal Growth Factor; D006493:Heparin