Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion.
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.
Brand
K
K
Institute of Clinical Chemistry and Pathobiochemistry, Technical University Munich, Germany.
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S
Rogler
G
G
Bartsch
A
A
Brandl
R
R
Knuechel
R
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M
M
Kaltschmidt
C
C
Baeuerle
P A
PA
Neumeier
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D
D000818:Animals; D000911:Antibodies, Monoclonal; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D004730:Endothelium, Vascular / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D015345:Oligonucleotide Probes / Q000235:genetics; D011499:Protein Processing, Post-Translational
D000911:Antibodies, Monoclonal; D007145:Immunoglobulin kappa-Chains; D016328:NF-kappa B; D015345:Oligonucleotide Probes