Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion

• Published in: The Journal of clinical investigation 1996-04, Vol.97 (7), p.1715-1722
• Main Authors: Brand, K, Page, S, Rogler, G, Bartsch, A, Brandl, R, Knuechel, R, Page, M, Kaltschmidt, C, Baeuerle, P A, Neumeier, D
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal; Arteriosclerosis - etiology; Arteriosclerosis - genetics; Arteriosclerosis - metabolism; Base Sequence; Endothelium, Vascular - metabolism; Gene Expression Regulation; Humans; Immunoglobulin kappa-Chains - genetics; Immunohistochemistry; Macrophages - metabolism; Mice; Models, Biological; Molecular Sequence Data; Muscle, Smooth, Vascular - metabolism; NF-kappa B - immunology; NF-kappa B - metabolism; Oligonucleotide Probes - genetics; Protein Processing, Post-Translational
• ISSN: 0021-9738
• DOI: 10.1172/jci118598

Nuclear factor-kappa B (NF-kappaB)/Rel transcription factors play an important role in the inducible regulation of a variety of genes involved in the inflammatory and proliferative responses of cells. The present study was designed to elucidate the implication of NF-kappaB/Rel in the pathogenesis of atherosclerosis. Activation of the dimeric NF-kappaB complex is regulated at a posttranslational level and requires the release of the inhibitor protein IkappaB. The newly developed mAb alpha-p65mAb recognizes the IkappaB binding region on the p65 (RelA) DNA binding subunit and therefore selectively reacts with p65 in activated NF-kappaB. Using immunofluorescence and immunohistochemical techniques, activated NF-kappaB was detected in the fibrotic-thickened intima/media and atheromatous areas of the atherosclerotic lesion. Activation of NF-kappaB was identified in smooth muscle cells, macrophages, and endothelial cells. Little or no activated NF-kappaB was detected in vessels lacking atherosclerosis. Electrophoretic mobility shift assays and colocalization of activated NF-kappaB with NF-kappaB target gene expression suggest functional implications for this transcription factor in the atherosclerotic lesion. This study demonstrates the presence of activated NF-kappaB in human atherosclerotic tissue for the first time. Atherosclerosis, characterized by features of chronic inflammation and proliferative processes, may be a paradigm for the involvement of NF-kappaB/Rel in chronic inflammatory disease.