Expression and function of anti-inflammatory interleukins: the other side of the vascular response to injury.
Expression and function of anti-inflammatory interleukins: the other side of the vascular response to injury.
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DOI：
10.2174/157016109788340721
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发表时间：
2009-07
影响因子：
4.5
通讯作者：
Autieri MV
中科院分区：
文献类型：
--
作者：
Cuneo AA;Autieri MV
常见于多种血管疾病，包括动脉粥样硬化、介入性再狭窄和移植血管病变，是局部炎症反应。活化的血管平滑肌细胞（VSMC）对局部炎症反应，并从中膜迁移到血管腔中，在那里它们增殖并合成细胞因子，它们以自分泌方式对细胞因子反应，维持病变的进展。促炎细胞因子，特别是免疫调节性白细胞介素，对血管病理生理学和这些适应不良过程的发展的有害影响一直是深入研究的主题。虽然大量的注意力已经给予了促炎细胞因子和白细胞介素的负面影响，相对较少的报道的潜在有益的旁分泌和自分泌的抗炎白细胞介素对血管损伤的反应。对抗炎介质的分泌和功能的绝大多数强调都放在白细胞上。因此，对非免疫细胞的作用和抗炎性白细胞介素对血管细胞的直接作用知之甚少。我们将综述抗炎白细胞介素抑制炎症细胞信号转导和基因表达的分子机制。我们将回顾一些研究，其中抗炎白细胞介素对血管疾病进展的有益“间接”作用是通过调节免疫功能实现的。我们还将介绍这些白细胞介素对VSMC和内皮细胞的“直接”作用抑制血管对损伤的反应的有限研究。我们认为，免疫调节细胞因子的表达激活血管系统可能代表一种自动调节反馈机制，以促进解决血管损伤的反应。
Common to multiple vascular diseases, including atherosclerosis, interventional restenosis, and transplant vasculopathy, is a localized inflammatory reaction. Activated vascular smooth muscle cells (VSMC) respond to local inflammation and migrate from the media into the lumen of the vessel where they proliferate and synthesize cytokines which they respond to in an autocrine fashion, sustaining the progression of the lesion. The deleterious effects of pro-inflammatory cytokines, particularly immunomodulatory interleukins, on vascular pathophysiology and development of these maladaptive processes have been the subject of intense study. Although a great deal of attention has been given to the negative effects of pro-inflammatory cytokines and interleukins, relatively little has been reported on the potentially beneficial paracrine and autocrine effects of anti-inflammatory interleukins on the vascular response to injury. The vast majority of emphasis on secretion and function of anti-inflammatory mediators has been placed on leukocytes. Consequently, the role of non-immune cells, and direct effects of anti-inflammatory interleukins on vascular cells is poorly understood. We will review the molecular mechanisms whereby anti-inflammatory interleukins inhibit signal transduction and gene expression in inflammatory cells. We will review studies in which beneficial “indirect” effects of anti-inflammatory interleukins on progression of vascular disease are achieved by modulation of immune function. We will also present the limited studies in which “direct” effects of these interleukins on VSMC and endothelial cells dampen the vascular response to injury. We propose that expression of immunomodulatory cytokines by activated vasculature may represent an auto-regulatory feed back mechanism to promote resolution of the vascular response to injury.
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