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

Nuclear factor-kappa B (NF-kappa B)/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-kappa B/Rel in the pathogenesis of atherosclerosis. Activation of the dimeric NF-kappa B complex is regulated at a posttranslational level and requires the release of the inhibitor protein I kappa B. The newly developed mAb alpha-p65mAb recognizes the I kappa B binding region on the p65 (RelA) DNA binding subunit and therefore selectively reacts with p65 in activated NF-kappa B. Using immunofluorescence and immunohistochemical techniques, activated NF-kappa B was detected in the fibrotic-thickened intima/media and atheromatous areas of the atherosclerotic lesion. Activation of NF-kappa B was identified in smooth muscle cells, macrophages, and endothelial cells. Little or no activated NF-kappa B was detected in vessels lacking atherosclerosis. Electrophoretic mobility shift assays and colocalization of activated NF-kappa B with NF-kappa B target gene expression suggest functional implications for this transcription factor in the atherosclerotic lesion. This study demonstrates the presence of activated NF-kappa B 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-kappa B/Rel in chronic inflammatory disease.