期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2004
卷号:101
期号:15
页码:5634-5639
DOI:10.1073/pnas.0401060101
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Nuclear factor {kappa}B (NF-{kappa}B) activation has been observed in human atherosclerotic plaques and is enhanced in unstable coronary plaques, but whether such activation has a protective or pathophysiological role remains to be determined. We addressed this question by developing a short-term culture system of cells isolated from human atherosclerotic tissue, allowing efficient gene transfer to directly investigate signaling pathways in human atherosclerosis. We found that NF-{kappa}B is activated in these cells and that this activity involves p65, p50, and c-Rel but not p52 or RelB. This NF-{kappa}B activation can be blocked by overexpression of I{kappa}B{alpha} or dominant-negative I{kappa}B kinase (IKK)-2 but not dominant-negative IKK-1 or NF-{kappa}B-inducing kinase, resulting in selective inhibition of inflammatory cytokines (tumor necrosis factor {alpha