IL-18 Accelerates Atherosclerosis Accompanied by Elevation of IFN- and CXCL16 Expression Independently of T Cells
IL-18 Accelerates Atherosclerosis Accompanied by Elevation of IFN- and CXCL16 Expression Independently of T Cells
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DOI：
10.1161/01.atv.0000153516.02782.65
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发表时间：
2005-04
期刊：
影响因子：
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通讯作者：
C. Tenger;A. Sundborger;J. Jawień;Xinghua Zhou
中科院分区：
文献类型：
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作者：
C. Tenger;A. Sundborger;J. Jawień;Xinghua Zhou
目的：IL-18的致动脉粥样硬化作用依赖于干扰素的产生。据认为，活化的T细胞通过分泌干扰素-α发挥致动脉粥样硬化的作用。然而，最近的体外研究表明，巨噬细胞、NK细胞，甚至血管平滑肌细胞也可以在IL-18等细胞因子的刺激下分泌干扰素。因此，我们在体内研究了在IL-18的刺激下，除了活化的T细胞外，其他细胞是否可以通过分泌干扰素发挥致动脉粥样硬化的作用。方法和结果：SCID/apoE基因敲除小鼠每周3次腹腔注射IL-18或磷酸盐缓冲液，共7周。我们的结果表明，尽管没有T细胞，但使用IL-18会导致3倍大的病变和2倍高的循环干扰素。此外，在皮损和脾中都观察到了干扰素-α的增加，并伴随着清道夫受体/趋化因子CXCL16的升高。此外，我们的研究结果表明，在体内没有T细胞的情况下，巨噬细胞、NK细胞和血管细胞是IL-18刺激下产生干扰素的来源。结论：目前的数据表明，在没有T细胞的情况下，IL-18的促动脉粥样硬化作用可以发生，巨噬细胞、NK细胞和血管细胞分泌的干扰素足以促进疾病的进展。
Objective—The proatherogenic effect of IL-18 is shown to be dependent on IFN- production. It is believed that activated T cells play a proatherogenic role through secretion of IFN-. However, recent studies in vitro have shown that macrophages, NK cells, and even vascular smooth muscle cells may also secrete IFN- after stimulation by cytokines like IL-18. We therefore investigated whether cells other than activated T cells can play a proatherogenic role via IFN- 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- despite the absence of T cells. In addition, increased IFN-, 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- under the stimulation of IL-18 in the absence of T cells in vivo. Conclusion—The current data suggest that the proatherogenic effect of IL-18 can occur in the absence of T cells and that IFN- secreted by macrophages, NK cells, and vascular cells is sufficient for the disease progression.