Expression of NF-kappa B and I kappa B-alpha by aortic endothelium in an arterial injury model.
Endothelial cells at sites of inflammatory responses express a variety of genes that are under the control of nuclear factor NF-kappa B, a transcription factor that with its inhibitors may be linked in an autoregulatory system that can be activated by multiple signals relevant to vascular pathophysiology. A model of limited endothelial denudation in the aorta of rats and mice was used to study the role of NF-kappa B and the inhibitor I kappa B-alpha Using en face techniques for in situ hybridization and immunostaining, normal endothelium showed diffuse cytoplasmic immunoreactivity for the NF-kappa B components p50 and p65 as well as the inhibitor I kappa B-alpha Within 45 minutes after wounding, nuclear staining for both NF-kappa B components was noticeable in the endothelial cells at the wound edge, which was followed by a dramatic induction of VCAM-1 mRNA and protein 3 hours later. Leading edge endothelial cells also responded with up-regulated expression of both NF-kappa B components and I kappa B-alpha. The increased expression of p50, p65, VCAM-1, and I kappa B-alpha persisted in replicating endothelium that was associated with adhesion of monocyte/macrophages to these cells. Expression levels returned to normal after regeneration. Our data establish for the first time the presence of the NF-kappa B/I kappa B-alpha system in the vasculature and demonstrate a correlation between activation of the regulatory system and induction of a kappa B-dependent endothelial adhesion molecule in an animal model of arterial injury. This autoregulatory system may be an important homeostatic mechanism in the vessel wall.
Lindner
V
V
Department of Pathology, University of Washington, Seattle, USA.
Collins
T
T
D000818:Animals; D001011:Aorta / Q000293:injuries / Q000378:metabolism*; D002448:Cell Adhesion; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004195:Disease Models, Animal; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D020672:I-kappa B Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007962:Leukocytes / Q000502:physiology; D008297:Male; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000096:biosynthesis*; D052002:NF-kappa B p50 Subunit; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051996:Transcription Factor RelA; D015533:Transcriptional Activation / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D004268:DNA-Binding Proteins; D019040:E-Selectin; D020672:I-kappa B Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D019010:Vascular Cell Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha