{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:52:47Z","timestamp":1791420767742,"version":"4.3.3"},"reference-count":61,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,2,18]]},"abstract":"<jats:p>\n                    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 \u03baB (NF-\u03baB). Therefore, NF-\u03baB is a good candidate to convert psychosocial stress into cellular activation. Volunteers were subjected to a brief laboratory stress test and NF-\u03baB 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-\u03baB 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-\u03baB-controlled \u03b2-globin transgene were stressed by immobilization. Immobilization resulted in increased \u03b2-globin expression, which could be reduced in the presence of the \u03b11-adrenergic inhibitor prazosin. To define the role of adrenergic stimulation in the up-regulation of NF-\u03baB, 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-\u03baB and NF-\u03baB-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 \u03b1\n                    <jats:sub>1<\/jats:sub>\n                    - and \u03b2-adrenergic inhibitors. Thus, noradrenaline-dependent adrenergic stimulation results in activation of NF-\u03baB\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Activation of NF-\u03baB 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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0438019100","type":"journal-article","created":{"date-parts":[[2003,2,18]],"date-time":"2003-02-18T15:04:50Z","timestamp":1045580690000},"page":"1920-1925","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":748,"title":["A mechanism converting psychosocial stress into mononuclear cell activation"],"prefix":"10.1073","volume":"100","author":[{"given":"Angelika","family":"Bierhaus","sequence":"first","affiliation":[{"name":"Department of Medicine I and Department of Neurology, University of Heidelberg, Otto-Meyerhof-Zentrum, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany; Institute of Experimental Psychology II, University of D\u00fcsseldorf, Universit\u00e4tsstrasse 1, 40225 D\u00fcsseldorf, Germany; Department of Psychology, University of Kiel, Olshausenstrasse 40, 24098 Kiel, Germany; and Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutta","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Medicine I and Department of Neurology, University of Heidelberg, Otto-Meyerhof-Zentrum, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany; Institute of Experimental Psychology II, University of D\u00fcsseldorf, Universit\u00e4tsstrasse 1, 40225 D\u00fcsseldorf, Germany; Department of Psychology, University of Kiel, Olshausenstrasse 40, 24098 Kiel, Germany; and Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Andrassy","sequence":"additional","affiliation":[{"name":"Department of Medicine 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