A mechanism converting psychosocial stress into mononuclear cell activation

Angelika Bierhaus*, Jutta Wolf, Martin Andrassy, Nicolas Rohleder, Per M. Humpert, Dimitri Petrov, Roman Ferstl, Maximilian Von Eynatten, Thoralf Wendt, Gottfried Rudofsky, Martina Joswig, Michael Morcos, Markus Schwaninger, Bruce McEwen, Clemens Kirschbaum, Peter P. Nawroth

*Corresponding author for this work
529 Citations (Scopus)


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 KB (NF-κB). Therefore, NF-κB is a good candidate to convert psychosocial stress into cellular activation. Volunteers were subjected to a brief laboratory stress test and NF-κB 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-κB 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-κB-controlled β-globin transgene were stressed by immobilization. Immobilization resulted in increased β-globin expression, which could be reduced in the presence of the α1-adrenergic inhibitor prazosin. To define the role of adrenergic stimulation in the up-regulation of NF-κB, 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-κB and NF-κB-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 α1- and β-adrenergic inhibitors. Thus, noradrenaline-dependent adrenergic stimulation results in activation of NF-κB in vitro and in vivo. Activation of NF-κB 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.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number4
Pages (from-to)1920-1925
Number of pages6
Publication statusPublished - 18.02.2003

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


Dive into the research topics of 'A mechanism converting psychosocial stress into mononuclear cell activation'. Together they form a unique fingerprint.

Cite this