title: Adrenergic receptors mediate stress-induced elevations in extracellular Hsp72.
abstract: Heat-shock protein concentrations in the blood increase after exposure to a variety of stressors, including trauma and psychological stress. Although the physiological function of extracellular heat shock protein remains controversial, there is evidence that extracellular heat shock protein 72 (Hsp72) can facilitate immunologic responses. The signal(s) that mediate(s) the in vivo elevation of extracellular Hsp72 in the blood after stressor exposure remain(s) unknown. Here we report that Hsp72 increases in the circulation via an alpha1-adrenergic receptor-mediated signaling pathway. Activation of alpha1-adrenoceptors results in a rapid increase in circulating Hsp72, and blockade of alpha1-adrenoceptors prevents the stress-induced rise in circulating Hsp72. Furthermore, our studies exclude a role for beta-adrenoceptors, glucocorticoids, and ACTH in mediating stress-induced elevations in circulating extracellular Hsp72. Understanding the signals involved in elevating extracellular Hsp72 could facilitate the use of extracellular Hsp72 to bolster immunity and perhaps prevent exacerbation of inflammatory diseases during stress.
authors.affiliation: Center for Neuroscience, Dept. of Integrative Physiology, Univ. of Colorado at Boulder, Boulder, CO 80309-0354, USA. john.johnson@colorado.edu
authors.forename: John D
authors.initials: JD
authors.lastname: Johnson
authors.forename: Jay
authors.initials: J
authors.lastname: Campisi
authors.forename: Craig M
authors.initials: CM
authors.lastname: Sharkey
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Kennedy
authors.forename: Molly
authors.initials: M
authors.lastname: Nickerson
authors.forename: Monika
authors.initials: M
authors.lastname: Fleshner
mesh_terms: D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D004597:Electroshock; D005110:Extracellular Space / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism*; D007016:Hypophysectomy; D007107:Immune System / Q000502:physiology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological / Q000276:immunology / Q000378:metabolism*; D014443:Tyrosine / Q000493:pharmacokinetics
chemical_list: D002395:Catecholamines; D005938:Glucocorticoids; D050884:HSP72 Heat-Shock Proteins; D018340:Receptors, Adrenergic, alpha-1; D014443:Tyrosine; D000324:Adrenocorticotropic Hormone