title: The nuclear factor-kappa B/inhibitor of kappa B autoregulatory system and atherosclerosis.
abstract: Nuclear factor-kappa B is a ubiquitous transcription factor that can be activated by diverse proatherogenic stimuli such as inflammatory cytokines, lipopolysaccharide, oxidant stress and physical forces. Recently, there have been major advances in understanding signal transduction from the tumor necrosis factor receptor, a model activator of the nuclear factor-kappa B system. One set of signals from the receptor initiates a phosphorylation cascade resulting in the activation of a kinase complex which phosphorylates an inhibitor of nuclear factor-kappa B, or inhibitor of kappa B. Degradation of the inhibitor occurs in parallel with activation and nuclear accumulation of the transcription factor. Subsequent changes in gene expression induce the production of multiple cytokines and adhesion molecules, which are important in early atherosclerotic lesion formation, and generation of survival signals, which could be important in lesion progression. A second set of signals from the tumor necrosis factor receptor leads to cell death. Understanding these competing pathways in vascular cells may help to clarify the role of this transcription factor in the proliferative lesions of atherogenesis.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Thurberg
authors.forename: T
authors.initials: T
authors.lastname: Collins
mesh_terms: D001161:Arteriosclerosis / Q000209:etiology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D016923:Cell Death; D016207:Cytokines / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism; D005786:Gene Expression Regulation; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor