van Es T, van Puijvelde G H M, Ramos O H, Segers F M E, Joosten L A, van den Berg W B, Michon I M, de Vos P, van Berkel Th J C, Kuiper J
Division of Biopharmaceutics, Leiden Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
Biochem Biophys Res Commun. 2009 Oct 16;388(2):261-5. doi: 10.1016/j.bbrc.2009.07.152. Epub 2009 Aug 4.
Atherosclerosis is an inflammatory disease characterized by the influx of macrophages and T cells and IL-17 may connect innate and adaptive immune responses involved in atherogenesis. We investigated the role of IL-17 receptor signaling in atherosclerosis and transplanted LDLr deficient recipient mice with IL-17R deficient bone marrow. Induction of atherosclerosis by Western-type diet induced a 46% reduction in lesion size in the aortic root and the plaque composition revealed no significant changes in collagen content and neutrophil counts, but a reduction in mast cell number and an increase in macrophage number. In addition, we observed a decrease in anti-oxLDL antibodies of the IgG class upon IL-17R BMT, while introduction of IL-17R deficient bone marrow resulted in a reduced IL-6 production and an increased IL-10 production. In conclusion, signaling via the IL-17 receptor in bone marrow derived cells enhances the process of atherosclerosis.
动脉粥样硬化是一种以巨噬细胞、T细胞浸润为特征的炎症性疾病,白细胞介素-17(IL-17)可能将参与动脉粥样硬化形成的固有免疫应答和适应性免疫应答联系起来。我们研究了IL-17受体信号传导在动脉粥样硬化中的作用,并将IL-17R缺陷的骨髓移植到低密度脂蛋白受体(LDLr)缺陷的受体小鼠体内。西式饮食诱导动脉粥样硬化,导致主动脉根部病变大小减少46%,斑块成分显示胶原含量和中性粒细胞计数无显著变化,但肥大细胞数量减少,巨噬细胞数量增加。此外,我们观察到IL-17R骨髓移植后IgG类抗氧化型低密度脂蛋白(oxLDL)抗体减少,而引入IL-17R缺陷骨髓导致IL-6产生减少,IL-10产生增加。总之,骨髓来源细胞中通过IL-17受体的信号传导会增强动脉粥样硬化进程。