IL-33 reduces the development of atherosclerosis.
IL-33 reduces the development of atherosclerosis.
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DOI：
10.1084/jem.20071868
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发表时间：
2008-02-18
期刊：
影响因子：
--
通讯作者：
Liew FY
中科院分区：
文献类型：
--
作者：
Miller AM;Xu D;Asquith DL;Denby L;Li Y;Sattar N;Baker AH;McInnes IB;Liew FY
动脉粥样硬化是血管系统的慢性炎症性疾病，通常导致心肌梗死和中风。我们发现，IL-33，这是一种新的IL-1样细胞因子，通过ST 2信号，可以减少高脂饮食ApoE−/−小鼠动脉粥样硬化的发展。IL-33和ST 2存在于小鼠和人的正常和动脉粥样硬化血管系统中。尽管对照PBS处理的小鼠在主动脉窦中形成严重的和发炎的动脉粥样硬化斑块，但在IL-33处理的动物中病变发展显著减少。IL-33还显著增加血清和淋巴结细胞中IL-4、IL-5和IL-13的水平，但降低IFNγ的水平。IL-33治疗还升高了总血清伊加、IgE和IgG 1的水平，但降低了IgG 2a，这与Th 1至Th 2的转换一致。IL-33治疗的小鼠也产生了显着升高的抗氧化低密度脂蛋白（ox-LDL）抗体。相反，与对照IgG处理的小鼠相比，用可溶性ST 2（一种中和IL-33的诱饵受体）处理的小鼠在ApoE−/−小鼠的主动脉窦中形成了显著更大的动脉粥样硬化斑块。此外，抗IL-5 mAb与IL-33共同给药可防止斑块大小减小，并减少IL-33诱导的ox-LDL抗体量。结论：IL-33可能通过诱导IL-5和ox-LDL抗体在动脉粥样硬化的发展中发挥保护作用。
Atherosclerosis is a chronic inflammatory disease of the vasculature commonly leading to myocardial infarction and stroke. We show that IL-33, which is a novel IL-1–like cytokine that signals via ST2, can reduce atherosclerosis development in ApoE−/− mice on a high-fat diet. IL-33 and ST2 are present in the normal and atherosclerotic vasculature of mice and humans. Although control PBS-treated mice developed severe and inflamed atherosclerotic plaques in the aortic sinus, lesion development was profoundly reduced in IL-33–treated animals. IL-33 also markedly increased levels of IL-4, -5, and -13, but decreased levels of IFNγ in serum and lymph node cells. IL-33 treatment also elevated levels of total serum IgA, IgE, and IgG1, but decreased IgG2a, which is consistent with a Th1-to-Th2 switch. IL-33–treated mice also produced significantly elevated antioxidized low-density lipoprotein (ox-LDL) antibodies. Conversely, mice treated with soluble ST2, a decoy receptor that neutralizes IL-33, developed significantly larger atherosclerotic plaques in the aortic sinus of the ApoE−/− mice compared with control IgG-treated mice. Furthermore, coadministration of an anti–IL-5 mAb with IL-33 prevented the reduction in plaque size and reduced the amount of ox-LDL antibodies induced by IL-33. In conclusion, IL-33 may play a protective role in the development of atherosclerosis via the induction of IL-5 and ox-LDL antibodies.
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