Extracellular matrix components prevent lipopolysaccharide-induced bovine arterial endothelial cell injury by inhibiting p38 mitogen-activated protein kinase.
The effect of extracellular matrix components on lipopolysaccharide-induced vascular endothelial cell injury was studied by using lipopolysaccharide-susceptible bovine aortic endothelial cells. For evaluation of lipopolysaccharide-induced injury, we estimated DNA synthesis and cell detachment of bovine aortic endothelial cells in cultures using extracellular matrix components-coated plastic dishes. Among extracellular matrix components, matrigel almost completely inhibited the reduction in DNA synthesis and the enhancement in cell detachment of bovine aortic endothelial cells in cultures with lipopolysaccharide. The lipopolysaccharide-induced injury was also inhibited by coating with type IV collagen, gelatin, fibronectin, laminin, vitronectin, and heparin sulphate proteoglycan. Extracellular matrix components capable of preventing lipopolysaccharide-induced bovine aortic endothelial cells injury coincidentally inhibited the phosphorylation of p38 mitogen-activated protein kinase in lipopolysaccharide-treated bovine aortic endothelial cells. SB203580, a specific inhibitor of p38 mitogen-activated protein kinase, also prevented the reduction in DNA synthesis and the enhancement in cell detachment of bovine aortic endothelial cells in cultures with lipopolysaccharide. It was therefore suggested that extracellular matrix components might protect bovine aortic endothelial cells from lipopolysaccharide-induced injury through inhibiting the activation of p38 mitogen-activated protein kinase.
Chakravortty
D
D
Department of Microbiology and Immunology, and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University, Nagakute, Aichi, Japan.
Kato
Y
Y
Koide
N
N
Sugiyama
T
T
Kawai
M
M
Fukada
M
M
Yoshida
T
T
Yokochi
T
T
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D007093:Imidazoles; D008070:Lipopolysaccharides; D011725:Pyridines; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580