1. IL-18 accelerates atherosclerosis accompanied by elevation of IFN-gamma and CXCL16 expression independently of T cells.
- Author
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Tenger C, Sundborger A, Jawien J, and Zhou X
- Subjects
- Animals, Apolipoproteins E genetics, Arteriosclerosis metabolism, Arteriosclerosis physiopathology, Chemokine CXCL16, Chemokine CXCL6, Chemokines, CXC metabolism, Endothelium, Vascular immunology, Endothelium, Vascular metabolism, Female, Gene Expression drug effects, Gene Expression immunology, Interferon-gamma metabolism, Interleukin-18 immunology, Killer Cells, Natural immunology, Killer Cells, Natural metabolism, Macrophages immunology, Macrophages metabolism, Membrane Proteins metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, SCID, Receptors, Immunologic metabolism, Receptors, Scavenger, Spleen immunology, Spleen metabolism, Arteriosclerosis immunology, Chemokines, CXC genetics, Interferon-gamma genetics, Interleukin-18 pharmacology, Membrane Proteins genetics, Receptors, Immunologic genetics, T-Lymphocytes immunology
- Abstract
Objective: The proatherogenic effect of IL-18 is shown to be dependent on IFN-gamma production. It is believed that activated T cells play a proatherogenic role through secretion of IFN-gamma. However, recent studies in vitro have shown that macrophages, NK cells, and even vascular smooth muscle cells may also secrete IFN-gamma after stimulation by cytokines like IL-18. We therefore investigated whether cells other than activated T cells can play a proatherogenic role via IFN-gamma secretion under the stimulation of IL-18 in vivo., Methods and Results: SCID/apoE knockout mice were injected intraperitoneally with either IL-18 or phosphate-buffered saline 3 times per week for 7 weeks. Our results show that administration of IL-18 leads to 3-fold larger lesions and 2-fold higher circulating IFN-gamma despite the absence of T cells. In addition, increased IFN-gamma, accompanied by elevation of the scavenger receptor/chemokine CXCL16, was observed in both lesions and spleens. Furthermore, our findings revealed that macrophages, NK cells, and vascular cells were the source of IFN-gamma under the stimulation of IL-18 in the absence of T cells in vivo., Conclusions: The current data suggest that the proatherogenic effect of IL-18 can occur in the absence of T cells and that IFN-gamma secreted by macrophages, NK cells, and vascular cells is sufficient for the disease progression.
- Published
- 2005
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