Department of Regenerative Cardiology, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor Fernandez Almagro 3, E-28029 Madrid, Spain.
Cardiovasc Res. 2010 May 1;86(2):283-92. doi: 10.1093/cvr/cvq050. Epub 2010 Feb 17.
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.
损伤因子引起的炎症反应受到严格调控，以避免白细胞聚集不当或无法解决而产生的不良后果。脂多糖（LPS）激活的内皮细胞通过控制膜相关黏附分子的表达将白细胞募集到炎症组织中。已知整合素连接激酶（ILK）调节巨噬细胞中的 LPS 反应；在这项研究中，我们研究了 ILK 在调节内皮细胞中 LPS 引发的炎症反应中的作用。
这项研究是在从肺和冠状动脉血管中分离的永生化小鼠内皮细胞（EC）上进行的。对细胞进行了全面表征，并通过 siRNA 和 shRNA 技术抑制 ILK 表达来研究 ILK 在调节 LPS 反应中的作用。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、细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）的表达。ILK 敲低通过阻止 ICAM-1 和 VCAM-1 的诱导，损害了 LPS 介导的内皮细胞激活。阻断 LPS 诱导的反应抑制了白细胞与内皮细胞牢固黏附和跨内皮迁移的炎症相关过程。
ILK 参与了受炎症刺激 LPS 激活的 EC 细胞黏附分子的表达。这种表达的减少调节了白细胞与内皮细胞的黏附和渗出过程。这一发现表明，ILK 可能成为炎症相关疾病血管特异性治疗中抗炎的潜在靶点。
