Interleukin-24 Suppresses the Growth of Vascular Smooth Muscle Cells by Inhibiting H2O2-Induced Reactive Oxygen Species Production
Interleukin-24 Suppresses the Growth of Vascular Smooth Muscle Cells by Inhibiting H2O2-Induced Reactive Oxygen Species Production
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DOI：
10.1159/000343242
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发表时间：
2012-01-01
期刊：
影响因子：
3.1
通讯作者：
Kang, Hyung-Sik
中科院分区：
文献类型：
--
作者：
Lee, Ki-Mo;Kang, Haeng-A.;Kang, Hyung-Sik
背景/目的：活性氧（reactive oxygen species， ROS）诱导的血管平滑肌细胞（vascular smooth muscle cells, VSMCs）异常生长被认为是血管疾病的一个重要致病过程。白细胞介素(IL)-24通过诱导细胞周期阻滞和凋亡特异性抑制癌细胞生长。然而，IL-24在ros诱导的VSMC生长中的作用尚未被研究。方法：采用MTT法、基因表达法、流式细胞术和抓伤愈合法检测IL-24对h2o2处理小鼠血管主动脉平滑肌（MOVAS）细胞的抗生长作用。为了阐明IL-24在ros诱导的信号传导中的作用，采用Western blot分析。结果：IL-24通过调控p21和cyclin D1，诱导细胞周期阻滞在G(0)/G(1)期，从而抑制H2O2作用下正常MOVAS细胞的生长。此外，IL-24抑制血管内皮生长因子和血小板源性生长因子的mRNA表达，从而降低细胞对H2O2的迁移水平。有趣的是，IL-24通过减少线粒体H2O2的产生和增强抗氧化酶的表达来减弱H2O2诱导的ROS产生。我们还发现H2O2诱导PI3K/Akt和Erk信号通路的能力被IL-24阻断。结论：IL-24可能通过调控线粒体ROS的产生和抗氧化酶的表达，抑制h2o2诱导的正常VSMCs的生长。巴塞尔S. Karger股份有限公司版权所有
Background/Aim: The abnormal growth of vascular smooth muscle cells (VSMCs) induced by reactive oxygen species (ROS) is considered a major pathogenic process in vascular diseases. Interleukin (IL)-24 specifically inhibits cancer cell growth through the induction of cell cycle arrest and apoptosis. However, the role of IL-24 in ROS-induced VSMC growth has not yet been investigated. Methods: An MTT assay, gene expression analysis, flow cytometry and a scratch wound healing assay were performed to determine the anti-growth effects of IL-24 in H2O2-treated mouse vascular aortic smooth muscle (MOVAS) cells. To elucidate the effect of IL-24 on ROS-induced signaling, Western blot analysis was employed. Results: IL-24 inhibited the growth of normal MOVAS cells treated with H2O2 by inducing a cell cycle arrest at the G(0)/G(1) phase through the regulation of p21 and cyclin D1. Furthermore, IL-24 suppressed mRNA expression of vascular endothelial growth factor and platelet-derived growth factor and subsequently decreased the level of cell migration in response to H2O2. Interestingly, IL-24 attenuated the H2O2-induced ROS production by reducing the mitochondrial H2O2 production and enhancing the expression of antioxidant enzymes. We also showed that the ability of H2O2 to induce the PI3K/Akt and Erk signaling pathways was blocked by IL-24. Conclusion: These findings suggest a novel mechanism in which IL-24 suppresses the growth of normal VSMCs by inhibiting H2O2-induced ROS production through the regulation of mitochondrial ROS production and expression of antioxidant enzymes. Copyright (C) 2012 S. Karger AG, Basel