ILK mediates LPS-induced vascular adhesion receptor expression and subsequent leucocyte trans-endothelial migration†
ILK mediates LPS-induced vascular adhesion receptor expression and subsequent leucocyte trans-endothelial migration†
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DOI：
10.1093/cvr/cvq050
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发表时间：
2010-05-01
影响因子：
10.8
通讯作者：
Luque, Alfonso
中科院分区：
文献类型：
--
作者：
Hortelano, Sonsoles;Lopez-Fontal, Raquel;Luque, Alfonso
对有害物质的炎症反应受到严格调节，以避免不适当的白细胞积聚或未能解决的不良后果。脂多糖（LPS）激活的内皮通过控制膜相关粘附分子的表达将白细胞募集到炎症组织。巨噬细胞中的LPS反应是由整合素连接激酶（ILK）调节的，在本研究中，我们研究了ILK在调节LPS诱导的内皮细胞炎症反应中的作用。彻底表征细胞，并通过使用siRNA和shRNA技术抑制ILK表达来研究ILK在LPS应答调节中的作用。表型和功能分析证实，永生化细胞表现为真正的EC。LPS诱导炎症基因E-选择素、细胞间粘附分子-1（ICAM-1）和血管细胞粘附分子-1（VCAM-1）的表达。ILK敲低通过阻止ICAM-1和VCAM-1的诱导而损害LPS介导的内皮活化。阻断LPS诱导的反应可抑制炎症相关的白细胞粘附和跨内皮迁移过程。ILK参与炎症刺激LPS激活EC表达细胞粘附分子。这种减少的表达调节白细胞粘附到内皮和外渗过程。这一发现表明ILK是开发炎症相关疾病血管特异性治疗的潜在抗炎靶点。
The inflammatory response to injurious agents is tightly regulated to avoid adverse consequences of inappropriate leucocyte accumulation or failed resolution. Lipopolysaccharide (LPS)-activated endothelium recruits leucocytes to the inflamed tissue through controlled expression of membrane-associated adhesion molecules. LPS responses in macrophages are known to be regulated by integrin-linked kinase (ILK); in this study, we investigated the role of ILK in the regulation of the LPS-elicited inflammatory response in endothelium.This study was performed on immortalized mouse endothelial cells (EC) isolated from lung and coronary vasculature. Cells were thoroughly characterized and the role of ILK in the regulation of the LPS response was investigated by suppressing ILK expression using siRNA and shRNA technologies. Phenotypic and functional analyses confirmed that the immortalized cells behaved as true EC. LPS induced the expression of the inflammatory genes E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). ILK knockdown impaired LPS-mediated endothelial activation by preventing the induction of ICAM-1 and VCAM-1. Blockade of the LPS-induced response inhibited the inflammatory-related processes of firm adhesion and trans-endothelial migration of leucocytes.ILK is involved in the expression of cell adhesion molecules by EC activated with the inflammatory stimulus LPS. This reduced expression modulates leucocyte adhesion to the endothelium and the extravasation process. This finding suggests ILK as a potential anti-inflammatory target for the development of vascular-specific treatments for inflammation-related diseases.