title: ILK mediates LPS-induced vascular adhesion receptor expression and subsequent leucocyte trans-endothelial migration.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Regenerative Cardiology, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor Fernandez Almagro 3, E-28029 Madrid, Spain.
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Hortelano
authors.forename: Raquel
authors.initials: R
authors.lastname: López-Fontal
authors.forename: Paqui G
authors.initials: PG
authors.lastname: Través
authors.forename: Natividad
authors.initials: N
authors.lastname: Villa
authors.forename: Carsten
authors.initials: C
authors.lastname: Grashoff
authors.forename: Lisardo
authors.initials: L
authors.lastname: Boscá
authors.forename: Alfonso
authors.initials: A
authors.lastname: Luque
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019169:Jurkat Cells; D036904:Leukocyte Rolling / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011070:Poly I-C / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D018836:Inflammation Mediators; D018799:Intercellular Adhesion Molecule-1; D008070:Lipopolysaccharides; D011070:Poly I-C; D017346:Protein Serine-Threonine Kinases; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D000099200:Scaffold Protein ILK