Brand K, Page S, Rogler G, Bartsch A, Brandl R, Knuechel R, Page M, Kaltschmidt C, Baeuerle P A, Neumeier D
Institute of Clinical Chemistry and Pathobiochemistry, Technical University Munich, Germany.
J Clin Invest. 1996 Apr 1;97(7):1715-22. 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.
核因子-κB（NF-κB）/Rel转录因子在诱导调控多种参与细胞炎症和增殖反应的基因中发挥重要作用。本研究旨在阐明NF-κB/Rel在动脉粥样硬化发病机制中的意义。二聚体NF-κB复合物的激活在翻译后水平受到调控，并且需要抑制蛋白IκB的释放。新开发的单克隆抗体α-p65mAb识别p65（RelA）DNA结合亚基上的IκB结合区域，因此在活化的NF-κB中与p65选择性反应。使用免疫荧光和免疫组织化学技术，在动脉粥样硬化病变的纤维化增厚内膜/中膜和动脉粥样硬化区域检测到活化的NF-κB。在平滑肌细胞、巨噬细胞和内皮细胞中鉴定出NF-κB的激活。在没有动脉粥样硬化的血管中几乎检测不到或未检测到活化的NF-κB。电泳迁移率变动分析以及活化的NF-κB与NF-κB靶基因表达的共定位表明该转录因子在动脉粥样硬化病变中具有功能意义。本研究首次证明人动脉粥样硬化组织中存在活化的NF-κB。以慢性炎症和增殖过程为特征的动脉粥样硬化可能是NF-κB/Rel参与慢性炎症性疾病的一个范例。
