摘要
不同细胞因子和趋化因子的复杂网络调节动脉粥样硬化的,一种慢性炎症疾病。白细胞介素17A(IL-17A)是由CD4 + IL-17 + T细胞(Th17),γδT细胞,天然杀伤细胞,天然杀伤T细胞和嗜中性粒细胞等不同白细胞亚群表达。IL-17A在宿主防御中起着重要的作用并且参与不同自身免疫和炎症疾病的病理学。近期的研究表明了IL-17A与动脉粥样有关。IL-17A似乎在动脉粥样硬化的形成具有主要的促炎作用,尽管在部分文献对此有争议。在鼠系统中,几项研究指出IL-17A可通过增加白细胞(特别是巨噬细胞)的迁移到动脉粥样硬化病变中介导IL-17A的促动脉粥样硬化作用,使用Apoe增强促炎细胞因子和趋化因子以及斑块去稳定基质金属蛋白酶的表达-/- 和低密度蛋白-/-小鼠。相比之下,三项研究显示IL-17A通过下调主动脉VCAM--1表达对内皮细胞的介导,并增加LDLr-/-小鼠血管平滑肌细胞(VSMCs)的胶原蛋白的产生。在人类中,IL-17A的表达与人类动脉粥样硬化病变的炎症和斑块易感性增加有关。此外,IL-17A诱导人斑块组织样品的炎性环境的促炎,前血栓形成,斑块去稳定和细胞吸引反应。值得注意的是,最近发表的一项研究通过显示IL-17A血清水平低的急性心肌梗死患者的较差结果来挑战这些发现。在以下的综述中,我们重点介绍了动脉粥样硬化中IL-17A功能研究的最新进展,并将尝试收集有争议的数据的解释。
关键词: 包细胞介素-17A, 亲动脉粥样硬化,抗动脉粥样硬化,斑块脆弱性,动脉粥样硬化,发炎
Current Drug Targets
Title:The Two Faces of Interleukin-17A in Atherosclerosis
Volume: 18 Issue: 7
关键词: 包细胞介素-17A, 亲动脉粥样硬化,抗动脉粥样硬化,斑块脆弱性,动脉粥样硬化,发炎
摘要: A complex network of different cytokines and chemokines modulates atherosclerosis, a chronic inflammatory disease. Interleukin-17A (IL-17A) is expressed by different leukocyte subsets such as CD4+IL-17+ T cells (Th17), γδ T cells, natural killer cells, natural killer T cells, and neutrophils. IL-17A plays an important role in host defense and is involved in the pathology of different autoimmune and inflammatory diseases. Recent studies demonstrate an association of IL-17A with atherosclerosis. IL-17A seems to have primarily pro-inflammatory effects in atherogenesis, although there are partially controversial results in the literature. In the murine system, several studies indicate a pro-atherogenic role of IL-17A mediated by increased migration of leukocytes (especially macrophages) into atherosclerotic lesions, increased expression of pro-inflammatory cytokines and chemokines as well as plaque destabilizing matrix-metalloproteinases using Apoe-/- and LDLr-/- mice. In contrast, three studies show atheroprotective effects of IL-17A mediated by downregulation of aortic VCAM-1 expression on endothelial cells and increased collagen production by vascular smooth muscle cells (VSMCs) in LDLr-/- mice. In humans, expression of IL-17A was associated with increased inflammation and plaque vulnerability in human atherosclerotic lesions. Moreover, IL-17A induced a pro-inflammatory, pro-thrombotic, plaque-destabilizing, and cell-attracting response of the inflammatory milieu of human plaque tissue samples. Notably, a recently published study challenged these findings by showing a worse outcome of patients with acute myocardial infarction with low serum levels of IL-17A. In the following review, we will focus on the recent progress of functional studies of IL-17A in atherosclerosis and will try to collect explanations for the controversial data.
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The Two Faces of Interleukin-17A in Atherosclerosis, Current Drug Targets 2017; 18 (7) . https://dx.doi.org/10.2174/1389450117666161229142155
DOI https://dx.doi.org/10.2174/1389450117666161229142155 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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