title: A mechanism converting psychosocial stress into mononuclear cell activation.
abstract: 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 kappaB (NF-kappaB). Therefore, NF-kappaB is a good candidate to convert psychosocial stress into cellular activation. Volunteers were subjected to a brief laboratory stress test and NF-kappaB 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-kappaB 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-kappaB-controlled beta-globin transgene were stressed by immobilization. Immobilization resulted in increased beta-globin expression, which could be reduced in the presence of the alpha1-adrenergic inhibitor prazosin. To define the role of adrenergic stimulation in the up-regulation of NF-kappaB, 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-kappaB and NF-kappaB-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 alpha(1)- and beta-adrenergic inhibitors. Thus, noradrenaline-dependent adrenergic stimulation results in activation of NF-kappaB in vitro and in vivo. Activation of NF-kappaB 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.
authors.affiliation: Department of Medicine I, University of Heidelberg, Otto-Meyerhof-Zentrum, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany. angelika.bierhaus@med.uni-heidelberg.de
authors.forename: Angelika
authors.initials: A
authors.lastname: Bierhaus
authors.forename: Jutta
authors.initials: J
authors.lastname: Wolf
authors.forename: Martin
authors.initials: M
authors.lastname: Andrassy
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rohleder
authors.forename: Per M
authors.initials: PM
authors.lastname: Humpert
authors.forename: Dimitri
authors.initials: D
authors.lastname: Petrov
authors.forename: Roman
authors.initials: R
authors.lastname: Ferstl
authors.forename: Maximilian
authors.initials: M
authors.lastname: von Eynatten
authors.forename: Thoralf
authors.initials: T
authors.lastname: Wendt
authors.forename: Gottfried
authors.initials: G
authors.lastname: Rudofsky
authors.forename: Martina
authors.initials: M
authors.lastname: Joswig
authors.forename: Michael
authors.initials: M
authors.lastname: Morcos
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaninger
authors.forename: Bruce
authors.initials: B
authors.lastname: McEwen
authors.forename: Clemens
authors.initials: C
authors.lastname: Kirschbaum
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004837:Epinephrine / Q000097:blood; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000097:blood / Q000276:immunology*
chemical_list: D017931:DNA Primers; D016328:NF-kappa B; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine