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

K Brand, S Page, G Rogler, A Bartsch… - The Journal of …, 1996 - Am Soc Clin Investig
K Brand, S Page, G Rogler, A Bartsch, R Brandl, R Knuechel, M Page, C Kaltschmidt…
The Journal of clinical investigation, 1996Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation