利用新型人源化转基因小鼠模型鉴定人类 IL-8 在血管狭窄中的功能特性。

IF 3.5 3区 医学 Q2 PHARMACOLOGY & PHARMACY
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引用次数: 0

摘要

IL-8(又名白细胞介素 8,CXCL8)是一种在病变血管壁中高表达的原型细胞因子,其血浆浓度与心血管事件密切相关。然而,IL-8 是否在心血管疾病中起到致病作用,目前仍是一个未知数。在这项研究中,我们使用了一种在基因组中整合了细菌人工染色体(BAC)的人类 IL-8 转基因(Tg)小鼠品系。该 BAC 包括 166 kb 的序列,涵盖人类 IL-8 基因座以及含有调控元件的上下游 DNA 序列。该 BAC 确保了小鼠体内人 IL-8 的病理生理调控表达,而不是强制组成型表达。Tg 小鼠受到颈动脉完全结扎损伤。从损伤后 3 天到 2 周,IL-8 在结扎损伤的颈动脉中高度表达。因此,在 Tg 小鼠中观察到新内膜增生加剧,Mac2 和 PCNA 阳性细胞增多。为了进一步证实 IL-8 在促进新内膜形成中的作用,在结扎部位用抗 IL-8 治疗中和了 IL-8。结果,新生内膜的大小明显缩小。我们的研究结果为IL-8在血管损伤反应和新内膜形成过程中的调控和功能提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Functional characterization of human IL-8 in vascular stenosis using a novel humanized transgenic mouse model

Functional characterization of human IL-8 in vascular stenosis using a novel humanized transgenic mouse model
IL-8 (aka interleukin 8, CXCL8) is a prototypic cytokine that is highly expressed in the diseased vessel wall and its plasma concentration is strongly associated with cardiovascular events. However, whether IL-8 plays a causative role in cardiovascular diseases remains largely unknown. In this study we used a human IL-8 transgenic (Tg) mouse strain with a bacterial artificial chromosome (BAC) integrated into its genome. This BAC encompasses 166 kb of sequence encompassing the human IL-8 gene locus as well as upstream and downstream DNA sequences containing regulatory elements. This BAC ensured a pathophysiologically regulated, rather than forced constitutive, expression of human IL-8 in the mouse. Tg mice were subjected to complete carotid ligation injury. IL-8 was highly expressed in the ligation-injured carotid artery from 3 days until 2 weeks after injury. As a result, exacerbated neointimal hyperplasia and increased Mac2 and PCNA positive cells were observed in Tg mice. To further confirm its role in promoting neointimal formation, IL-8 was neutralized by anti-IL8 treatment at the ligation site. Consequently, the size of neointima was significantly reduced. Our results provided new insights into the regulation and function of IL-8 in response to vascular insult and during neointima formation.
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来源期刊
Vascular pharmacology
Vascular pharmacology 医学-药学
CiteScore
6.60
自引率
2.50%
发文量
153
审稿时长
31 days
期刊介绍: Vascular Pharmacology publishes papers, which contains results of all aspects of biology and pharmacology of the vascular system. Papers are encouraged in basic, translational and clinical aspects of Vascular Biology and Pharmacology, utilizing approaches ranging from molecular biology to integrative physiology. All papers are in English. The Journal publishes review articles which include vascular aspects of thrombosis, inflammation, cell signalling, atherosclerosis, and lipid metabolism.
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