Interleukin-10 blocks atherosclerotic events in vitro and in vivo
Interleukin-10 blocks atherosclerotic events in vitro and in vivo
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DOI：
10.1161/01.atv.19.12.2847
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发表时间：
1999-12-01
影响因子：
8.7
通讯作者：
Fyfe, AI
中科院分区：
文献类型：
--
作者：
Oslund, LJP;Hedrick, CC;Fyfe, AI
动脉粥样硬化可以部分被视为一种炎症性疾病过程，因此可能容易受到免疫状态的操纵。白细胞介素 10 (IL-10) 是一种由活化的淋巴细胞和单核细胞产生的抑制性细胞因子。这些研究提供的证据表明，IL-10 可以抑制最低限度氧化的 LDL (MM-LDL) 诱导的单核细胞-内皮细胞相互作用，并抑制动脉粥样硬化饮食小鼠中动脉粥样硬化病变的形成。用重组 IL-10 预处理人主动脉内皮细胞 (HAEC) 18 小时，而不是 4 小时，导致 MM-LDL 诱导的单核细胞结合显着减少。研究发现 IL-10 在 10 ng/mL 时效果最大。用有义但非反义方向表达病毒 bcrf-1 IL-10 (Ad-vIL-10) 的腺病毒转染 HAEC 完全抑制 MM-LDL 诱导单核细胞结合的能力。在用氧化 1-棕榈酰-2-花生四烯酰-sn-甘油-3-磷酸胆碱 (OxPAPC) 刺激的 HAEC 中使用 IL-10 或 Ad-vIL-10 获得了类似的结果。我们之前已经表明 cAMP 的增加与内皮细胞的 MM-LDL 激活相关。 MM-LDL 诱导的 cAMP 水平增加不会因与 IL-10 预孵育而受到抑制，体内研究表明，与致动脉粥样化饮食的对照组相比，在人 IL-2 启动子控制下具有鼠 IL-10 转基因的小鼠的病变减少（5433+/-4008 mm(2) 对比 13574+/-4212 mm(2)；P
Atherosclerosis can be viewed in part as an inflammatory disease process and may therefore be susceptible to manipulation of the immune state. Interleukin 10 (IL-10) is an inhibitory cytokine produced by activated lymphocytes and monocytes. These studies present evidence that IL-10 can inhibit minimally oxidized LDL (MM-LDL)-induced monocyte-endothelium interaction as well as inhibit atherosclerotic lesion formation in mice fed an atherosclerotic diet, Pretreatment of human aortic endothelial cells (HAECs) for 18, but not 4, hours with recombinant IL-10 caused a significant decrease in MM-LDL-induced monocyte binding. IL-10 was found to be maximally effective at 10 ng/mL. Transfection of HAECs with adenovirus expressing viral bcrf-1 IL-10 (Ad-vIL-10) in a sense but not antisense orientation completely inhibited the ability of MM-LDL to induce monocyte binding. Similar results were obtained with IL-10 or Ad-vIL-10 in HAECs stimulated with oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorycholine (OxPAPC), We have previously shown increases in cAMP associated with MM-LDL activation of endothelial cells. The MM-LDL-induced increase in cAMP levels was not inhibited by preincubation with IL-10, In vivo studies demonstrated that mice with a murine IL-10 transgene under the control of the human IL-2 promoter have decreased lesions versus controls on an atherogenic diet (5433+/-4008 mm(2) versus 13574+/-4212 mm(2); P