Lipopolysaccharide activates matrix metalloproteinase-2 in endothelial cells through an NF-kappaB-dependent pathway.
Vascular endothelial cells release proteinases that degrade the extracellular matrix, thus enabling cell migration during angiogenesis and vasculogenesis. Endothelial cells secrete mainly the proform of matrix metalloproteinase-2 (proMMP-2). In this report, we examined several growth factors, cytokines, and other molecules for activation of MMP-2 by human umbilical vein endothelial cells. Of these factors, we found that lipopolysaccharide (LPS) is the strongest activator of MMP-2. LPS induced MMP-2 activation in a time- and dose-dependent manner. While pretreatment with zinc chelators or nuclear factor kappaB (NF-kappaB) inhibitors suppressed LPS-induced MMP-2 activation, pretreatment with phosphatidylinositol 3'-kinase inhibitors had no effect. These results indicate that, in endothelial cells, LPS can directly enhance angiogenesis by inducing MMP-2 activation mediated through an NF-kappaB pathway.
Kim
H
H
National Creative Research Initiatives Center for Cardiac Regeneration and Institute of Cardiovascular Research, Chonbuk National University School of Medicine, Chonju, 560-180, Korea.
Koh
G
G
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic; D000081082:Phosphoinositide-3 Kinase Inhibitors
D008070:Lipopolysaccharides; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020778:Matrix Metalloproteinase 2