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：2003
卷号：100
期号：4
页码：1920-1925
DOI：10.1073/pnas.0438019100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Little is known about the mechanisms converting psychosocial stress into cellular dysfunction. Various genes, up-regulated in atherosclerosis but also by psychosocial stress, are controlled by the transcription factor nuclear factor {kappa}B (NF-{kappa}B). Therefore, NF-{kappa}B is a good candidate to convert psychosocial stress into cellular activation. Volunteers were subjected to a brief laboratory stress test and NF-{kappa}B activity was determined in peripheral blood mononuclear cells (PBMC), as a window into the body and because PBMC play a role in diseases such as atherosclerosis. In 17 of 19 volunteers, NF-{kappa}B was rapidly induced during stress exposure, in parallel with elevated levels of catecholamines and cortisol, and returned to basal levels within 60 min. To model this response, mice transgenic for a strictly NF-{kappa}B-controlled {beta}-globin transgene were stressed by immobilization. Immobilization resulted in increased {beta}-globin expression, which could be reduced in the presence of the 1-adrenergic inhibitor prazosin. To define the role of adrenergic stimulation in the up-regulation of NF-{kappa}B, THP-1 cells were induced with physiological amounts of catecholamines for 10 min. Only noradrenaline resulted in a dose- and time-dependent induction of NF-{kappa}B and NF-{kappa}B-dependent gene expression, which depended on pertussis-toxin-sensitive G protein-mediated phosphophatidylinositol 3-kinase, Ras/Raf, and mitogen-activated protein kinase activation. Induction was reduced by 1- and {beta}-adrenergic inhibitors. Thus, noradrenaline-dependent adrenergic stimulation results in activation of NF-{kappa}B in vitro and in vivo. Activation of NF-{kappa}B represents a downstream effector for the neuroendocrine response to stressful psychosocial events and links changes in the activity of the neuroendocrine axis to the cellular response.
