An Interleukin-6 Receptor Antibody Suppresses Atherosclerosis in Atherogenic Mice.
An Interleukin-6 Receptor Antibody Suppresses Atherosclerosis in Atherogenic Mice.
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DOI：
10.3389/fcvm.2017.00084
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发表时间：
2017
影响因子：
3.6
通讯作者：
Daida H
中科院分区：
文献类型：
--
作者：
Akita K;Isoda K;Sato-Okabayashi Y;Kadoguchi T;Kitamura K;Ohtomo F;Shimada K;Daida H
IκBNS 是一种核 IκB 蛋白，可负调节核因子-κB 活性。我们证明，IκBNS 缺陷通过增加巨噬细胞产生白细胞介素 (IL)-6 来加速 LDL 受体缺陷 (LDLr−/−) 小鼠的动脉粥样硬化。先前的研究表明IL-6的增加可能有助于动脉粥样硬化病变的发展。然而，抗小鼠IL-6受体抗体（MR16-1）是否可以保护致动脉粥样硬化小鼠的动脉粥样硬化病变仍有待阐明。我们研究了 LDLr−/− 和 IκBNS−/−/LDLr−/− 小鼠在食用高脂肪饮食 16 周后的动脉粥样硬化病变。所有小鼠在高脂肪饮食期间每周接受一次 MR16-1 或磷酸盐缓冲盐水 (PBS)（对照）腹腔注射。 MR16-1 的治疗没有产生不良的全身效应，并且我们检测到两组的血清胆固醇水平没有显着差异。与 LDLr−/− 小鼠相比，在 PBS 治疗下，IκBNS−/−/LDLr−/− 小鼠的动脉粥样硬化病变显着增加（p< 0.01）。然而，MR16-1治疗消除了IκBNS−/−/LDLr−/−和LDLr−/−小鼠之间动脉粥样硬化病变的显着差异。有趣的是，与 PBS 治疗相比，MR16-1 还显着减少了 LDLr−/− 小鼠的动脉粥样硬化病变（p<0.05）。免疫染色显示，与PBS处理的小鼠相比，MR16-1处理的IκBNS−/−/LDLr−/−和LDLr−/−小鼠的动脉粥样硬化病变中磷酸STAT3阳性细胞百分比显着减少，表明MR16-1可以通过抑制IL-6–STAT3信号通路来抑制动脉粥样硬化病变。这项研究强调了抗 IL-6 疗法在预防血脂异常和/或炎症引起的动脉粥样硬化方面的潜在治疗益处。
IκBNS is a nuclear IκB protein which negatively regulates nuclear factor-κB activity. We demonstrated that IκBNS deficiency accelerates atherosclerosis in LDL receptor-deficient (LDLr−/−) mice via increased interleukin (IL)-6 production by macrophages. Previous studies showed that the increase in IL-6 might contribute to the development of atherosclerotic lesions. However, whether an anti-mouse IL-6 receptor antibody (MR16-1) can protect atherosclerotic lesions in atherogenic mice remains to be elucidated. We investigated atherosclerotic lesions in LDLr−/− and IκBNS−/−/LDLr−/− mice after 16 weeks consumption of a high-fat diet. All mice received intraperitoneal injections of MR16-1 or phosphate-buffered saline (PBS) (control) once a week during a high-fat diet consumption. Treatment of MR16-1 yielded no adverse systemic effects, and we detected no significant differences in serum cholesterol levels in either group. The atherosclerotic lesions were significantly increased in IκBNS−/−/LDLr−/− compared with LDLr−/− mice (p < 0.01) under treatment of PBS. However, MR16-1 treatment abolished the significant difference of atherosclerotic lesions between IκBNS−/−/LDLr−/− and LDLr−/− mice. Interestingly, MR16-1 also significantly decreased atherosclerotic lesions in LDLr−/− mice compared with PBS treatment (p < 0.05). Immunostaining revealed percent phospho-STAT3-positive cell were significantly decreased in the atherosclerotic lesions of MR16-1 treated both IκBNS−/−/LDLr−/− and LDLr−/− mice compared with PBS-treated mice, indicating MR16-1 could suppress atherosclerotic lesions via the inhibition of IL-6–STAT3 signaling pathway. This study highlights the potential therapeutic benefit of anti-IL-6 therapy in preventing atherogenesis induced by dyslipidemia and/or inflammation.
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影响因子：
37.8
作者：
Schieffer, B;Schieffer, E;Drexler, H
通讯作者：
Drexler, H
影响因子：
4
作者：
Grote, K;Luchtefeld, M;Schieffer, B
通讯作者：
Schieffer, B
影响因子：
32.4
作者：
Kuwata, H;Matsumoto, M;Takeda, K
通讯作者：
Takeda, K
影响因子：
120.7
作者：
Lindmark, E;Diderholm, E;Siegbahn, A
通讯作者：
Siegbahn, A
DOI：
10.1161/01.atv.0000079512.66448.1d
发表时间：
2003-07-01
影响因子：
8.7
作者：
Luc, G;Bard, JM;Ducimetiere, P
通讯作者：
Ducimetiere, P