IL-17A is proatherogenic in high-fat diet-induced and Chlamydia pneumoniae infection-accelerated atherosclerosis in mice.
IL-17A is proatherogenic in high-fat diet-induced and Chlamydia pneumoniae infection-accelerated atherosclerosis in mice.
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DOI：
10.4049/jimmunol.1001879
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发表时间：
2010-11-01
期刊：
影响因子：
--
通讯作者：
Arditi M
中科院分区：
文献类型：
--
作者：
Chen S;Shimada K;Zhang W;Huang G;Crother TR;Arditi M
IL-17在动脉粥样硬化形成中的作用仍然存在争议。我们先前报道TLR/MyD 88信号通路在高脂饮食中起重要作用，以及肺炎衣原体（Cpn）感染介导的ApoE缺陷小鼠动脉粥样硬化加速。在这里，我们研究了IL-17 A在高脂饮食和Cpn诱导的动脉粥样硬化加速中的作用。与野生型C57 Bl/6对照小鼠相比，饲喂高脂饮食的IL-17 A −/−小鼠的主动脉窦斑块和主动脉病变大小和脂质成分以及病变中的巨噬细胞积聚显著减少。正如预期的那样，Cpn感染导致野生型小鼠动脉粥样硬化病变的大小和脂质含量显著增加。然而，IL-17 A −/−小鼠在Cpn感染后，尽管血液胆固醇水平相似，但与野生型对照组相比，病变大小的加速程度显著降低。此外，野生型而非IL-17 A −/−小鼠中的Cpn感染与血清IL-12 p40、CCL 2、INFγ浓度及其斑块中巨噬细胞数量的显著增加相关。此外，体外研究表明，IL-17 A激活血管内皮细胞，血管内皮细胞分泌细胞因子，进而增强骨髓巨噬细胞中的泡沫细胞形成。总之，我们的数据表明，IL-17 A是促动脉粥样硬化的，它在饮食诱导的动脉粥样硬化病变发展和Cpn感染介导的高脂饮食存在下动脉粥样硬化病变的加速中起重要作用。
The role of IL-17 in atherogenesis remains controversial. We previously reported that the TLR/MyD88 signaling pathway plays an important role in high–fat diet, as well as Chlamydophila pneumoniae (Cpn) infection-mediated acceleration of atherosclerosis in ApoE deficient mice. Here we investigated the role of the IL-17A in high-fat diet and Cpn-induced acceleration of atherosclerosis. The aortic sinus plaque and aortic lesion size and lipid composition as well as macrophage accumulation in the lesions were significantly diminished in IL-17A−/− mice fed high-fat diet compared to wild-type C57Bl/6 control mice. As expected, Cpn infection led to a significant increase in size and lipid content of the atherosclerotic lesions in wild-type mice. However, IL-17A−/− mice developed significantly less acceleration of lesion size following Cpn infection compared to wild-type control despite similar levels of blood cholesterol levels. Furthermore, Cpn infection in wild-type but not in IL-17A−/− mice was associated with significant increases in serum concentrations of IL-12p40, CCL2, INFγ and numbers of macrophages in their plaques. Additionally, in vitro studies suggest that IL-17A activates vascular endothelial cells, which secrete cytokines that in turn enhance foam cell formation in bone marrow macrophages. Taken together, our data suggest that IL-17A is pro-atherogenic and that it plays an important role in both diet-induced atherosclerotic lesion development, and Cpn infection-mediated acceleration of atherosclerotic lesions in the presence of high fat diet.
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DOI：
10.4049/jimmunol.181.10.7186
发表时间：
2008-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chen S;Sorrentino R;Shimada K;Bulut Y;Doherty TM;Crother TR;Arditi M
通讯作者：
Arditi M
影响因子：
5.3
作者：
Blessing, E;Campbell, LA;Kuo, CC
通讯作者：
Kuo, CC
急性冠脉综合征患者Th17/Treg失衡
影响因子：
8.6
作者：
Cheng, Xiang;Yu, Xian;Liao, Yu-hua
通讯作者：
Liao, Yu-hua
影响因子：
4.4
作者：
Erbel, Christian;Chen, Lili;Dengler, Thomas J.
通讯作者：
Dengler, Thomas J.
DOI：
10.1073/pnas.94.9.4642
发表时间：
1997-04-29
影响因子：
11.1
作者：
Dansky, HM;Charlton, SA;Smith, JD
通讯作者：
Smith, JD