Interleukin-5 is a potential mediator of angiotensin II-induced aneurysm formation in apolipoprotein E knockout mice.
Interleukin-5 is a potential mediator of angiotensin II-induced aneurysm formation in apolipoprotein E knockout mice.
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DOI：
10.1016/j.jss.2011.12.016
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Eagleton MJ
中科院分区：
文献类型：
--
作者：
Xu J;Ehrman B;Graham LM;Eagleton MJ
本研究的目的是评估实验性腹主动脉瘤（AAA）形成过程中Th 1和Th 2细胞因子的变化。通过输注血管紧张素II（Ang II，1000 ng/kg/min）在载脂蛋白E敲除小鼠中诱导AAA。在第0、7、14和28天（N=11/时间点）通过ELISA评估主动脉匀浆中的选定Th 1和Th 2细胞因子。另外的小鼠共同施用抗IgG（N=20）或抗IL-5（N=20），并在第28天评估AAA。检测主动脉匀浆中MMP-2和MMP-9的表达。用IL-5（0-40 ng/ml）处理小鼠主动脉SMC（MASMC）和腹膜衍生的巨噬细胞，并评估细胞提取物和培养基（0-48小时）的MMP-2和MMP-9表达。血管紧张素II输注与IL-5和IL-10（分别）增加3.4倍（P<0.01）和3.6倍（P<0.01），IL-6减少0.6倍（P <0.01）相关。抗IL-5（而非抗IgG）可改善Ang II诱导的AAA形成。MMP-2和MMP-9的上调观察到在淋巴瘤，但不是在从小鼠抗IL-5治疗的淋巴瘤。IL-5刺激MASMC 24小时后，MMP-2和MMP-9 mRNA（分别为2.1倍和2.7倍，P<0.01）和蛋白（分别为1.6倍和1.9倍，P<0.01）增加。IL-5刺激巨噬细胞并不改变MMP的表达。在实验性AAA形成过程的早期，Ang II诱导增加的Th 2细胞因子IL-5和IL-10，并且抑制IL-5防止AAA形成，这表明了重要的作用。虽然IL-5能够上调MASMC中MMP-2和MMP-9的表达，但有必要研究AAA形成中的替代作用。
The aim of the study was to evaluate alterations in Th1 and Th2 cytokines during experimental abdominal aortic aneurysm (AAA) formation. AAAs were induced in apolipoprotein E null mice by infusing angiotensin II (Ang II, 1000 ng/kg/min). Aortic homogenates were assessed at 0, 7, 14, and 28 days (N=11/time point) for select Th1 and Th2 cytokines by ELISA. Additional mice had co-administration of anti-IgG (N=20) or anti-IL-5 (N=20) and were assessed at 28 days for AAA. Aortic homogenates were assessed forMMP-2 and MMP-9 expression. Mouse aortic SMC (MASMC) and peritoneal-derived macrophages were treated with IL-5 (0–40 ng/ml), and cell extracts and media (0–48 hours) were assessed for MMP-2 and MMP-9 expression. Ang II infusion was associated with a 3.4-fold (P<.01) and 3.6-fold (P<.01) increase in IL-5 and IL-10 (respectively), and a 0.6-fold reduction in IL-6, by 7 days. Anti-IL-5, but not anti-IgG, ameliorated Ang II-induced AAA formation. Upregulation of MMP-2 and MMP-9 was observed in aneurysmal aortas, but not in the aortas obtained from mice treated with anti-IL-5. IL-5 stimulation of MASMC increased MMP-2 and MMP-9 mRNA (2.1-fold and 2.7-fold, respectively, P<.01) and protein (1.6-fold and 1.9-fold, respectively, P<.01) by 24 hours. IL-5 stimulation of macrophages did not alter MMP expression. Ang II induces increased Th2 cytokines IL-5 and IL-10 early in the course of experimental AAA formation, and inhibition of IL-5 prevents AAA formation suggesting an important role.. While IL-5 is capable of upregulating MMP-2 and MMP-9 expression in MASMC, investigations into alternate roles in AAA formation is warranted.
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影响因子：
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