Differential Effects of IFN-β on the Survival and Growth of Human Vascular Smooth Muscle and Endothelial Cells.
Differential Effects of IFN-β on the Survival and Growth of Human Vascular Smooth Muscle and Endothelial Cells.
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DOI：
10.1089/biores.2014.0052
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发表时间：
2015
影响因子：
--
通讯作者：
Ueda T
中科院分区：
文献类型：
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作者：
Sano E;Tashiro S;Tsumoto K;Ueda T
已有文献证明干扰素-β在动物模型中对动脉粥样硬化或增生性动脉疾病的发生有一定的抑制作用。其作用机制主要是抑制血管平滑肌细胞(SMC)的生长。为了更好地了解其作用机制，我们详细研究了干扰素-β对血管内皮细胞(EC)和血管内皮细胞(EC)生长和凋亡的影响。干扰素-β促进血清饥饿培养上清液中系膜细胞的凋亡。反之，干扰素-β可抑制血清和生长因子剥夺诱导的内皮细胞凋亡。SMC对EC的诱导凋亡和抗凋亡作用与促凋亡基因Bax的表达和caspase-3活性有关。抗凋亡基因bcl2mRNA在EC中表达上调。干扰素-β以剂量依赖的方式抑制系膜细胞的生长。但低剂量的干扰素对EC的生长有明显的促进作用。其抗SMC增殖作用与激活p21、增加G0/G1期阻滞细胞有关。认为其对EC的生长促进作用可能与其增加S和G2/M期细胞有关。SMC产生干扰素-β，对各种刺激物作出反应。但EC不能诱导产生干扰素-β。提示SMC产生的内源性干扰素-β可能作用于EC，影响EC的功能。本研究阐明了干扰素-β可促进血管内皮细胞的凋亡，抑制内皮细胞的凋亡，促进内皮细胞的生长。这些作用被认为有助于治疗增生性动脉疾病，这是干扰素-β有效的机制。
It has been documented that interferon (IFN)-β is effective against the genesis of atherosclerosis or hyperplastic arterial disease in animal model. The main mechanism of the efficacy was antiproliferative action on the growth of vascular smooth muscle cells (SMC). To understand more about the mechanisms that are responsible for the efficacy, we examined minutely the effects of IFN-β on the apoptosis and growth of vascular SMC and endothelial cells (EC). IFN-β enhanced SMC apoptosis in serum starved medium. Conversely, EC apoptosis induced by serum and growth factor deprivation was inhibited by IFN-β. The induction of SMC apoptosis and anti-apoptotic effect on EC linked to the expression of pro-apoptotic bax mRNA and caspase-3 activities. Anti-apoptotic bcl-2 mRNA was also up-regulated in EC. IFN-β inhibited SMC growth in a dose dependent manner. However, the growth of EC was rather enhanced by a low dose of IFNs. The antiproliferative effect on SMC associated with the activation of p21 and increase of G0/G1 arrested cells. The growth stimulation on EC was considered to link with increase of S and G2/M phase cells. SMC produced IFN-β in response to various stimulants. However, IFN-β was not induced in EC. These suggested that endogenous IFN-β from SMC may act on EC and affect to EC functions. In this study, it was clarified that IFN-β enhances SMC apoptosis and inhibits the EC apoptosis, and stimulates the EC growth. These effects were considered to contribute to a cure against hyperplastic arterial diseases as the mechanisms in the efficacy of IFN-β.